Multiple faces of dynamin-related protein 1 and its role in Alzheimer's disease pathogenesis

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1862, Issue 4, 2016, Pages 814-828

  Kandimalla, Ramesh ^a   Reddy, P Hemachandra ^a,b  

^a TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^b TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER SCHOOL OF MEDICINE   (United States)

Author keywords

Alzheimer's disease; CDK5; Drp1; GSK3 ; MiRNA; Mitochondria; P53

Indexed keywords

CYCLIN DEPENDENT KINASE 5; DYNAMIN I; DYNAMIN RELATED PROTEIN 1; GLYCOGEN SYNTHASE KINASE 3; MICRORNA; PROTEIN P53; TAU PROTEIN; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; CELL SURVIVAL; HUMAN; MITOCHONDRION; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; SUMOYLATION; UBIQUITINATION;

EID: 84958568728     PISSN: 09254439     EISSN: 1879260X     Source Type: Journal    
DOI: 10.1016/j.bbadis.2015.12.018     Document Type: Review

References (216)

1. Yan J., Liu X.H., Han M.Z., Wang Y.M., Sun X.L., Yu N., Li T., Su B., Chen Z.Y. Blockage of GSK3beta-mediated Drp1 phosphorylation provides neuroprotection in neuronal and mouse models of Alzheimer's disease. Neurobiol. Aging 2015, 36:211-227.
2. Wallace D.C. Bioenergetics in human evolution and disease: implications for the origins of biological complexity and the missing genetic variation of common diseases. Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 2013, 368:20120267.
3. Reddy P.H., Tripathi R., Troung Q., Tirumala K., Reddy T.P., Anekonda V., Shirendeb U.P., Calkins M.J., Reddy A.P., Mao P., Manczak M. Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer's disease: implications to mitochondria-targeted antioxidant therapeutics. Biochim. Biophys. Acta 2012, 1822:639-649.
4. Roy M., Reddy P.H., Iijima M., Sesaki H. Mitochondrial division and fusion in metabolism. Curr. Opin. Cell Biol. 2015, 33:111-118.
5. Binukumar B.K., Gupta N., Sunkaria A., Kandimalla R., Wani W.Y., Sharma D.R., Bal A., Gill K.D. Protective efficacy of coenzyme Q10 against DDVP-induced cognitive impairments and neurodegeneration in rats. Neurotox. Res. 2012, 21:345-357.
6. Reddy P.H., Reddy T.P., Manczak M., Calkins M.J., Shirendeb U., Mao P. Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases. Brain Res. Rev. 2011, 67:103-118.
7. Binukumar B.K., Bal A., Kandimalla R.J., Gill K.D. Nigrostriatal neuronal death following chronic dichlorvos exposure: crosstalk between mitochondrial impairments, alpha synuclein aggregation, oxidative damage and behavioral changes. Mol. Brain 2010, 3:35.
8. Beal M.F. Mitochondria take center stage in aging and neurodegeneration. Ann. Neurol. 2005, 58:495-505.
9. Reddy P.H., Beal M.F. Are mitochondria critical in the pathogenesis of Alzheimer's disease?. Brain Res. Brain Res. Rev. 2005, 49:618-632.
10. Lin M.T., Beal M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006, 443:787-795.
11. Reddy P.H. Amyloid precursor protein-mediated free radicals and oxidative damage: implications for the development and progression of Alzheimer's disease. J. Neurochem. 2006, 96:1-13.
12. Reddy P.H. Mitochondrial oxidative damage in aging and Alzheimer's disease: implications for mitochondrially targeted antioxidant therapeutics. J. Biomed. Biotechnol. 2006, 2006:31372.
13. Reddy P.H. Mitochondrial dysfunction in aging and Alzheimer's disease: strategies to protect neurons. Antioxid. Redox Signal. 2007, 9:1647-1658.
14. Reddy P.H. Mitochondrial medicine for aging and neurodegenerative diseases. Neruomol. Med. 2008, 10:291-315.
15. Reddy P.H. Amyloid beta, mitochondrial structural and functional dynamics in Alzheimer's disease. Exp. Neurol. 2009, 218:286-292.
16. Reddy P.H., Beal M.F. Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease. Trends Mol. Med. 2008, 14:45-53.
17. Swerdlow R.H. Mitochondria and cell bioenergetics: increasingly recognized components and a possible etiologic cause of Alzheimer's disease. Antioxid. Redox Signal. 2012, 16:1434-1455.
18. Elgass K., Pakay J., Ryan M.T., Palmer C.S. Recent advances into the understanding of mitochondrial fission. Biochim. Biophys. Acta 2013, 1833:150-161.
19. Hoppins S. The regulation of mitochondrial dynamics. Curr. Opin. Cell Biol. 2014, 29:46-52.
20. Wang X., Su B., Lee H.G., Li X., Perry G., Smith M.A., Zhu X. Impaired balance of mitochondrial fission and fusion in Alzheimer's disease. J. Neurosci. 2009, 29:9090-9103.
21. Suliman H.B., Piantadosi C.A. Mitochondrial quality control as a therapeutic target. Pharmacol. Rev. 2016, 68:20-48.
22. Yoon Y., Pitts K.R., Dahan S., McNiven M.A. A novel dynamin-like protein associates with cytoplasmic vesicles and tubules of the endoplasmic reticulum in mammalian cells. J. Cell Biol. 1998, 140:779-793.
23. Shin H.W., Shinotsuka C., Torii S., Murakami K., Nakayama K. Identification and subcellular localization of a novel mammalian dynamin-related protein homologous to yeast Vps1p and Dnm1p. J. Biochem. 1997, 122:525-530.
24. Imoto M., Tachibana I., Urrutia R. Identification and functional characterization of a novel human protein highly related to the yeast dynamin-like GTPase Vps1p. J. Cell Sci. 1998, 111:1341-1349.
25. Otsuga D., Keegan B.R., Brisch E., Thatcher J.W., Hermann G.J., Bleazard W., Shaw J.M. The dynamin-related GTPase, Dnm1p, controls mitochondrial morphology in yeast. J. Cell Biol. 1998, 143:333-349.
26. Sesaki H., Jensen R.E. Division versus fusion: Dnm1p and Fzo1p antagonistically regulate mitochondrial shape. J. Cell Biol. 1999, 147:699-706.
27. Bleazard W., McCaffery J.M., King E.J., Bale S., Mozdy A., Tieu Q., Nunnari J., Shaw J.M. The dynamin-related GTPase Dnm1 regulates mitochondrial fission in yeast. Nat. Cell Biol. 1999, 1:298-304.
28. Mozdy A.D., McCaffery J.M., Shaw J.M. Dnm1p GTPase-mediated mitochondrial fission is a multi-step process requiring the novel integral membrane component Fis1p. J. Cell Biol. 2000, 151:367-380.
29. Cerveny K.L., McCaffery J.M., Jensen R.E. Division of mitochondria requires a novel DMN1-interacting protein, Net2p. Mol. Biol. Cell 2001, 12:309-321.
30. Tieu Q., Nunnari J. Mdv1p is a WD repeat protein that interacts with the dynamin-related GTPase, Dnm1p, to trigger mitochondrial division. J. Cell Biol. 2000, 151:353-366.
31. Fekkes P., Shepard K.A., Yaffe M.P. Gag3p, an outer membrane protein required for fission of mitochondrial tubules. J. Cell Biol. 2000, 151:333-340.
32. Griffin E.E., Graumann J., Chan D.C. The WD40 protein Caf4p is a component of the mitochondrial fission machinery and recruits Dnm1p to mitochondria. J. Cell Biol. 2005, 170:237-248.
33. Cerveny K.L., Studer S.L., Jensen R.E., Sesaki H. Yeast mitochondrial division and distribution require the cortical num1 protein. Dev. Cell 2007, 12:363-375.
34. Hammermeister M., Schodel K., Westermann B. Mdm36 is a mitochondrial fission-promoting protein in Saccharomyces cerevisiae. Mol. Biol. Cell 2010, 21:2443-2452.
35. Klecker T., Scholz D., Fortsch J., Westermann B. The yeast cell cortical protein Num1 integrates mitochondrial dynamics into cellular architecture. J. Cell Sci. 2013, 126:2924-2930.
36. Lackner L.L. Determining the shape and cellular distribution of mitochondria: the integration of multiple activities. Curr. Opin. Cell Biol. 2013, 25:471-476.
37. Labrousse A.M., Zappaterra M.D., Rube D.A., van der Bliek A.M. C. elegans dynamin-related protein DRP-1 controls severing of the mitochondrial outer membrane. Mol. Cell 1999, 4:815-826.
38. Manczak M., Reddy P.H. Abnormal interaction between the mitochondrial fission protein Drp1 and hyperphosphorylated tau in Alzheimer's disease neurons: implications for mitochondrial dysfunction and neuronal damage. Hum. Mol. Genet. 2012, 21:2538-2547.
39. Manczak M., Sesaki H., Kageyama Y., Reddy P.H. Dynamin-related protein 1 heterozygote knockout mice do not have synaptic and mitochondrial deficiencies. Biochim. Biophys. Acta 2012, 1822:862-874.
40. Kageyama Y., Zhang Z., Sesaki H. Mitochondrial division: molecular machinery and physiological functions. Curr. Opin. Cell Biol. 2011, 427-434.
41. Smirnova E., Griparic L., Shurland D.L., van der Bliek A.M. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol. Biol. Cell 2001, 12:2245-2256.
42. Palmer C.S., Elgass K.D., Parton R.G., Osellame L.D., Stojanovski D., Ryan M.T. Adaptor proteins MiD49 and MiD51 can act independently of Mff and Fis1 in Drp1 recruitment and are specific for mitochondrial fission. J. Biol. Chem. 2011, 288:27584-27593.
43. DuBoff B., Feany M., Gotz J. Why size matters - balancing mitochondrial dynamics in Alzheimer's disease. Trends Neurosci. 2013, 36:325-335.
44. Uo T., Dworzak J., Kinoshita C., Inman D.M., Kinoshita Y., Horner P.J., Morrison R.S. Drp1 levels constitutively regulate mitochondrial dynamics and cell survival in cortical neurons. Exp. Neurol. 2009, 218:274-285.
45. Cha M.Y., Kim D.K., Mook-Jung I. The role of mitochondrial DNA mutation on neurodegenerative diseases. Exp. Mol. Med. 2015, 47.
46. Raturi A., Simmen T. Where the endoplasmic reticulum and the mitochondrion tie the knot: the mitochondria-associated membrane (MAM). Biochim. Biophys. Acta 2013, 213-224.
47. Simmen T., Lynes E.M., Gesson K., Thomas G. Oxidative protein folding in the endoplasmic reticulum: tight links to the mitochondria-associated membrane (MAM). Biochim. Biophys. Acta 2010, 1465-1473.
48. Renvoise B., Blackstone C. Emerging themes of ER organization in the development and maintenance of axons. Curr. Opin. Neurobiol. 2010, 531-537.
49. Area-Gomez E., Del Carmen Lara Castillo M., Tambini M.D., Guardia-Laguarta C., de Groof A.J., Madra M., Ikenouchi J., Umeda M., Bird T.D., Sturley S.L., Schon E.A. Upregulated function of mitochondria-associated ER membranes in Alzheimer disease. EMBO J. 2012, 4106-4123.
50. Hedskog L., Pinho C.M., Filadi R., Ronnback A., Hertwig L., Wiehager B., Larssen P., Gellhaar S., Sandebring A., Westerlund M., Graff C., Winblad B., Galter D., Behbahani H., Pizzo P., Glaser E., Ankarcrona M. Modulation of the endoplasmic reticulum-mitochondria interface in Alzheimer's disease and related models, proc. Natl. Acad. Sci. U S A 2013, 7916-7921.
51. Kornmann B., Currie E., Collins S.R., Schuldiner M., Nunnari J., Weissman J.S., Walter P. An ER-mitochondria tethering complex revealed by a synthetic biology screen. Science 2009, 325:477-481.
52. Dayanithi G., Chen-Kuo-Chang M., Viero C., Hamel C., Muller A., Lenaers G. Characterization of Ca2+ signalling in postnatal mouse retinal ganglion cells: involvement of OPA1 in Ca2+ clearance. Ophthalmic Genet. 2010, 53-65.
53. Kushnareva Y.E., Gerencser A.A., Bossy B., Ju W.K., White A.D., Waggoner J., Ellisman M.H., Perkins G., Bossy-Wetzel E. Loss of OPA1 disturbs cellular calcium homeostasis and sensitizes for excitotoxicity. Cell Death Differ. 2013, 353-365.
54. Singaravelu K., Nelson C., Bakowski D., de Brito O.M., Ng S.W., Di Capite J., Powell T., Scorrano L., Parekh A.B. Mitofusin 2 regulates STIM1 migration from the Ca2+ store to the plasma membrane in cells with depolarized mitochondria. J. Biol. Chem. 2011, 12189-12201.
55. Friedman J.R., Lackner L.L., West M., DiBenedetto J.R., Nunnari J., Voeltz G.K. ER tubules mark sites of mitochondrial division. Science 2011, 358-362.
56. Hayashi T., Rizzuto R., Hajnoczky G., Su T.P. MAM: more than just a housekeeper. Trends Cell Biol. 2009, 81-88.
57. Schon E.A., Przedborski S. Mitochondria: the next (neurode)generation. Neuron 2011, 1033-1053.
58. Burte F., Carelli V., Chinnery P.F., Yu-Wai-Man P. Disturbed mitochondrial dynamics and neurodegenerative disorders. Nat. Rev. Neurol. 2015, 11-24.
59. Ishihara N., Nomura M., Jofuku A., Kato H., Suzuki S.O., Masuda K., Otera H., Nakanishi Y., Nonaka I., Goto Y., Taguchi N., Morinaga H., Maeda M., Takayanagi R., Yokota S., Mihara K. Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice. Nat. Cell Biol. 2009, 11:958-966.
60. Wakabayashi J., Zhang Z., Wakabayashi N., Tamura Y., Fukaya M., Kensler T.W., Iijima M., Sesaki H. The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice. J. Cell Biol. 2009, 186:805-816.
61. Pitts K.R., Yoon Y., Krueger E.W., McNiven M.A. The dynamin-like protein DLP1 is essential for normal distribution and morphology of the endoplasmic reticulum and mitochondria in mammalian cells. Mol. Biol. Cell 1999, 10:4403-4417.
62. Smirnova E., Shurland D.L., Ryazantsev S.N., van der Bliek A.M. A human dynamin-related protein controls the distribution of mitochondria. J. Cell Biol. 1998, 143:351-358.
63. Chen H., Chan D.C. Mitochondrial dynamics-fusion, fission, movement, and mitophagy-in neurodegenerative diseases. Hum. Mol. Genet. 2009, 18:R169-R176.
64. Wang X., Su B., Fujioka H., Zhu X. Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer's disease patients. Am. J. Pathol. 2008, 173:470-482.
65. Wang X., Perry G., Smith M.A., Zhu X. Amyloid-beta-derived diffusible ligands cause impaired axonal transport of mitochondria in neurons. Neurodegener. Dis. 2010, 7:56-59.
66. Li Z., Okamoto K., Hayashi Y., Sheng M. The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 2004, 119:873-887.
67. Santel A., Frank S. Shaping mitochondria: the complex posttranslational regulation of the mitochondrial fission protein DRP1. IUBMB Life 2008, 60:448-455.
68. Westermann B. Mitochondrial fusion and fission in cell life and death. Nat. Rev. Mol. Cell Biol. 2010, 11:872-884.
69. Kann O., Kovacs R. Mitochondria and neuronal activity. Am. J. Physiol. Cell. Physiol. 2007, 292:C641-C657.
70. Stowers R.S., Megeath L.J., Gorska-Andrzejak J., Meinertzhagen I.A., Schwarz T.L. Axonal transport of mitochondria to synapses depends on milton, a novel Drosophila protein. Neuron 2002, 36:1063-1077.
71. Melov S. Modeling mitochondrial function in aging neurons. Trends Neurosci. 2004, 27:601-606.
72. Guo X., Macleod G.T., Wellington A., Hu F., Panchumarthi S., Schoenfield M., Marin L., Charlton M.P., Atwood H.L., Zinsmaier K.E. The GTPase dMiro is required for axonal transport of mitochondria to Drosophila synapses. Neuron 2005, 47:379-393.
73. Calkins M.J., Manczak M., Mao P., Shirendeb U., Reddy P.H. Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer's disease. Hum. Mol. Genet. 2011, 20:4515-4529.
74. Koch K.V., Suelmann R., Fischer R. Deletion of mdmB impairs mitochondrial distribution and morphology in Aspergillus nidulans. Cell Motil. Cytoskeleton 2003, 55:114-124.
75. Li X., Baumgart E., Morrell J.C., Jimenez-Sanchez G., Valle D., Gould S.J. PEX11 beta deficiency is lethal and impairs neuronal migration but does not abrogate peroxisome function. Mol. Cell. Biol. 2002, 22:4358-4365.
76. Koch A., Yoon Y., Bonekamp N.A., McNiven M.A., Schrader M. A role for Fis1 in both mitochondrial and peroxisomal fission in mammalian cells. Mol. Biol. Cell 2005, 16:5077-5086.
77. Reddy P.H. Increased mitochondrial fission and neuronal dysfunction in Huntington's disease: implications for molecular inhibitors of excessive mitochondrial fission. Drug Discov. Today 2014, 19:951-955.
78. Reddy P.H. Inhibitors of mitochondrial fission as a therapeutic strategy for diseases with oxidative stress and mitochondrial dysfunction. J. Alzheimers Dis. 2014, 40:245-256.
79. Cribbs J.T., Strack S. Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep. 2007, 8:939-944.
80. Chang C.R., Blackstone C. Drp1 phosphorylation and mitochondrial regulation. EMBO Rep. 2007, 8:1088-1089. (author reply 1089-1090).
81. Frank S., Gaume B., Bergmann-Leitner E.S., Leitner W.W., Robert E.G., Catez F., Smith C.L., Youle R.J. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev. Cell 2001, 1:515-525.
82. Sheridan C., Delivani P., Cullen S.P., Martin S.J. Bax- or Bak-induced mitochondrial fission can be uncoupled from cytochrome C release. Mol. Cell 2008, 31:570-585.
83. Wu S., Zhou F., Zhang Z., Xing D. Bax is essential for Drp1-mediated mitochondrial fission but not for mitochondrial outer membrane permeabilization caused by photodynamic therapy. J. Cell. Physiol. 2010, 226:530-541.
84. Olichon A., Baricault L., Gas N., Guillou E., Valette A., Belenguer P., Lenaers G. Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis. J. Biol. Chem. 2003, 278:7743-7746.
85. Frezza C., Cipolat S., Martins de Brito O., Micaroni M., Beznoussenko G.V., Rudka T., Bartoli D., Polishuck R.S., Danial N.N., De Strooper B., Scorrano L. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell 2006, 126:177-189.
86. Fu J., Yu H.M., Chiu S.Y., Mirando A.J., Maruyama E.O., Cheng J.G., Hsu W. Disruption of SUMO-specific protease 2 induces mitochondria mediated neurodegeneration. PLoS Genet. 2014, 10.
87. Anderson C.A., Blackstone C. SUMO wrestling with Drp1 at mitochondria. EMBO J. 2013, 32:1496-1498.
88. Otera H., Ishihara N., Mihara K. New insights into the function and regulation of mitochondrial fission. Biochim. Biophys. Acta 2013, 1833:1256-1268.
89. Strack S., Cribbs J.T. Allosteric modulation of Drp1 mechanoenzyme assembly and mitochondrial fission by the variable domain. J. Biol. Chem. 2012, 287:10990-11001.
90. Chang C.R., Blackstone C. Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1. Ann. N. Y. Acad. Sci. 2010, 1201:34-39.
91. Harder Z., Zunino R., McBride H. Sumo1 conjugates mitochondrial substrates and participates in mitochondrial fission. Curr. Biol. 2004, 14:340-345.
92. Zunino R., Schauss A., Rippstein P., Andrade-Navarro M., McBride H.M. The SUMO protease SENP5 is required to maintain mitochondrial morphology and function. J. Cell Sci. 2007, 120:1178-1188.
93. Zunino R., Braschi E., Xu L., McBride H.M. Translocation of SenP5 from the nucleoli to the mitochondria modulates DRP1-dependent fission during mitosis. J. Biol. Chem. 2009, 284:17783-17795.
94. Braschi E., Zunino R., McBride H.M. MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission. EMBO Rep. 2009, 10:748-754.
95. Wasiak S., Zunino R., McBride H.M. Bax/Bak promote sumoylation of DRP1 and its stable association with mitochondria during apoptotic cell death. J. Cell Biol. 2007, 177:439-450.
96. Fu J., Jiang M., Mirando A.J., Yu H.M., Hsu W. Reciprocal regulation of Wnt and Gpr177/mouse Wntless is required for embryonic axis formation. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:18598-18603.
97. Figueroa-Romero C., Iniguez-Lluhi J.A., Stadler J., Chang C.R., Arnoult D., Keller P.J., Hong Y., Blackstone C., Feldman E.L. SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the b domain and is linked to its activity cycle. FASEB J. 2009, 23:3917-3927.
98. Karbowski M., Neutzner A., Youle R.J. The mitochondrial E3 ubiquitin ligase MARCH5 is required for Drp1 dependent mitochondrial division. J. Cell Biol. 2007, 178:71-84.
99. Park Y.Y., Lee S., Karbowski M., Neutzner A., Youle R.J., Cho H. Loss of MARCH5 mitochondrial E3 ubiquitin ligase induces cellular senescence through dynamin-related protein 1 and mitofusin 1. J. Cell Sci. 2010, 123:619-626.
100. Park Y.Y., Nguyen O.T., Kang H., Cho H. MARCH5-mediated quality control on acetylated Mfn1 facilitates mitochondrial homeostasis and cell survival. Cell Death Dis 2014, 5.
101. Nakamura N., Kimura Y., Tokuda M., Honda S., Hirose S. MARCH-V is a novel mitofusin 2- and Drp1-binding protein able to change mitochondrial morphology. EMBO Rep. 2006, 7:1019-1022.
102. Sugiura A., Nagashima S., Tokuyama T., Amo T., Matsuki Y., Ishido S., Kudo Y., McBride H.M., Fukuda T., Matsushita N., Inatome R. MITOL regulates endoplasmic reticulum-mitochondria contacts via Mitofusin2. Mol. Cell 2013, 51:20-34.
103. Embi N., Rylatt D.B., Cohen P. Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur. J. Biochem. 1980, 107:519-527.
104. Fernandez-Nogales M., Hernandez F., Miguez A., Alberch J., Gines S., Perez-Navarro E., Lucas J.J. Decreased glycogen synthase kinase-3 levels and activity contribute to Huntington's disease. Hum. Mol. Genet. 2015, 24:5040-5052.
105. Reddy P.H. Amyloid beta-induced glycogen synthase kinase 3beta phosphorylated VDAC1 in Alzheimer's disease: implications for synaptic dysfunction and neuronal damage. Biochim. Biophys. Acta 2013, 1832:1913-1921.
106. Jope R.S., Johnson G.V. The glamour and gloom of glycogen synthase kinase-3. Trends Biochem. Sci. 2004, 29:95-102.
107. Hoeflich K.P., Luo J., Rubie E.A., Tsao M.S., Jin O., Woodgett J.R. Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation. Nature 2000, 406:86-90.
108. Jiang H., Guo W., Liang X., Rao Y. Both the establishment and the maintenance of neuronal polarity require active mechanisms: critical roles of GSK-3beta and its upstream regulators. Cell 2005, 120:123-135.
109. DaRocha-Souto B., Coma M., Perez-Nievas B.G., Scotton T.C., Siao M., Sanchez-Ferrer P., Hashimoto T., Fan Z., Hudry E., Barroeta I., Sereno L., Rodriguez M., Sanchez M.B., Hyman B.T., Gomez-Isla T. Activation of glycogen synthase kinase-3 beta mediates beta-amyloid induced neuritic damage in Alzheimer's disease. Neurobiol. Dis. 2012, 45:425-437.
110. Martinez A., Perez D.I. GSK-3 inhibitors: a ray of hope for the treatment of Alzheimer's disease?. J. Alzheimers Dis. 2008, 15:181-191.
111. Kremer A., Louis J.V., Jaworski T., Van Leuven F. GSK3 and Alzheimer's disease: facts and fiction. Front. Mol. Neurosci. 2011, 4:17.
112. Hernandez F., Lucas J.J., Avila J. GSK3 and tau: two convergence points in Alzheimer's disease. J. Alzheimers Dis. 2013, 33(Suppl. 1):S141-S144.
113. Al Sweidi S., Sanchez M.G., Bourque M., Morissette M., Dluzen D., Di Paolo T. Oestrogen receptors and signalling pathways: implications for neuroprotective effects of sex steroids in Parkinson's disease. J. Neuroendocrinol. 2012, 24:48-61.
114. Mishra R. Glycogen synthase kinase 3 Beta: can it be a target for oral cancer. Mol. Cancer 2010, 9:144.
115. Fung T.K., Gandillet A., So C.W. Selective treatments of mixed-lineage leukemia leukemic stem cells through targeting glycogen synthase kinase 3 and the canonical Wnt/beta-catenin pathway. Curr. Opin. Hematol. 2012, 19:280-286.
116. Mills C.N., Nowsheen S., Bonner J.A., Yang E.S. Emerging roles of glycogen synthase kinase 3 in the treatment of brain tumors. Front. Mol. Neurosci. 2011, 4:47.
117. Gao C., Holscher C., Liu Y., Li L. GSK3: a key target for the development of novel treatments for type 2 diabetes mellitus and Alzheimer disease. Rev. Neurosci. 2011, 23:1-11.
118. Wang H., Brown J., Martin M. Glycogen synthase kinase 3: a point of convergence for the host inflammatory response. Cytokine 2011, 53:130-140.
119. Bersani F.S., Iannitelli A., Pacitti F., Bersani G. Sleep and biorythm disturbances in schizophrenia, mood and anxiety disorders: a review. Riv Psichiatr 2012, 47:365-375.
120. Rasola A., Sciacovelli M., Pantic B., Bernardi P. Signal transduction to the permeability transition pore. FEBS Lett. 2010, 584:1989-1996.
121. Sofola O., Kerr F., Rogers I., Killick R., Augustin H., Gandy C., Allen M.J., Hardy J., Lovestone S., Partridge L. Inhibition of GSK-3 ameliorates Abeta pathology in an adult-onset Drosophila model of Alzheimer's disease. PLoS Genet. 2012, 6.
122. Hurtado D.E., Molina-Porcel L., Carroll J.C., Macdonald C., Aboagye A.K., Trojanowski J.Q., Lee V.M. Selectively silencing GSK-3 isoforms reduces plaques and tangles in mouse models of Alzheimer's disease. J. Neurosci. 2012, 32:7392-7402.
123. Maqboo M., Mobashir M., Hoda N. Pivotal role of glycogen synthase kinase-3: A therapeutic target for Alzheimer's disease. Eur. J. Med. Chem. 2016, 107:63-81.
124. Schenk D., Barbour R., Dunn W., Gordon G., Grajeda H., Guido T., Hu K., Huang J., Johnson-Wood K., Khan K., Kholodenko D., Lee M., Liao Z., Lieberburg I., Motter R., Mutter L., Soriano F., Shopp G., Vasquez N., Vandevert C., Walker S., Wogulis M., Yednock T., Games D., Seubert P. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999, 400:173-177.
125. Alvarez G., Munoz-Montano J.R., Satrustegui J., Avila J., Bogonez E., Diaz-Nido J. Lithium protects cultured neurons against beta-amyloid-induced neurodegeneration. FEBS Lett. 1999, 453:260-264.
126. Hoshi M., Sato M., Matsumoto S., Noguchi A., Yasutake K., Yoshida N., Sato K. Spherical aggregates of beta-amyloid (amylospheroid) show high neurotoxicity and activate tau protein kinase I/glycogen synthase kinase-3beta. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:6370-6375.
127. Wei H., Leeds P.R., Qian Y., Wei W., Chen R., Chuang D. Beta-amyloid peptide-induced death of PC 12 cells and cerebellar granule cell neurons is inhibited by long-term lithium treatment. Eur. J. Pharmacol. 2000, 392:117-123.
128. Hong Y.R., Chen C.H., Cheng D.S., Howng S.L., Chow C.C. Human dynamin-like protein interacts with the glycogen synthase kinase 3beta. Biochem. Biophys. Res. Commun. 1998, 249:697-703.
129. Chen C.H., Hwang S.L., Howng S.L., Chou C.K., Hong Y.R. Three rat brain alternative splicing dynamin-like protein variants: interaction with the glycogen synthase kinase 3beta and action as a substrate. Biochem. Biophys. Res. Commun. 2000, 268:893-898.
130. Chou C.H., Lin C.C., Yang M.C., Wei C.C., Liao H.D., Lin R.C., Tu W.Y., Kao T.C., Hsu C.M., Cheng J.T., Chou A.K., Lee C.I., Loh J.K., Howng S.L., Hong Y.R. GSK3beta-mediated Drp1 phosphorylation induced elongated mitochondrial morphology against oxidative stress. PLoS One 2012, 7.
131. Kashatus D.F., Lim K.H., Brady D.C., Pershing N.L., Cox A.D., Counter C.M. RALA and RALBP1 regulate mitochondrial fission at mitosis. Nat. Cell Biol. 2011, 13:1108-1115.
132. McGeer P.L., McGeer E.G. The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res. Brain Res. Rev. 1995, 21:195-218.
133. Zimmermann M., Borroni B., Cattabeni F., Padovani A., Di Luca M. Cholinesterase inhibitors influence APP metabolism in Alzheimer disease patients. Neurobiol. Dis. 2005, 19:237-242.
134. Zhu X., Lee H.G., Raina A.K., Perry G., Smith M.A. The role of mitogen-activated protein kinase pathways in Alzheimer's disease. Neurosignals 2002, 11:270-281.
135. Hirai K., Aliev G., Nunomura A., Fujioka H., Russell R.L., Atwood C.S., Johnson A.B., Kress Y., Vinters H.V., Tabaton M., Shimohama S., Cash A.D., Siedlak S.L., Harris P.L., Jones P.K., Petersen R.B., Perry G., Smith M.A. Mitochondrial abnormalities in Alzheimer's disease. J. Neurosci. 2001, 21:3017-3023.
136. Herrup K., Neve R., Ackerman S.L., Copani A. Divide and die: cell cycle events as triggers of nerve cell death. J. Neurosci. 2004, 24:9232-9239.
137. Tang M.X., Jacobs D., Stern Y., Marder K., Schofield P., Gurland B., Andrews H., Mayeux R. Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet 1996, 348:429-432.
138. Casadesus G., Smith M.A., Zhu X., Aliev G., Cash A.D., Honda K., Petersen R.B., Perry G. Alzheimer disease: evidence for a central pathogenic role of iron-mediated reactive oxygen species. J. Alzheimers Dis. 2004, 6:165-169.
139. Manczak M., Mao P., Calkins M.J., Cornea A., Reddy A.P., Murphy M.P., Szeto H.H., Park B., Reddy P.H. Mitochondria-targeted antioxidants protect against amyloid-beta toxicity in Alzheimer's disease neurons. J. Alzheimers Dis. 2010, 20(Suppl. 2):S609-S631.
140. Manczak M., Calkins M.J., Reddy P.H. Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease: implications for neuronal damage. Hum. Mol. Genet. 2011, 20:2495-2509.
141. Kandimalla R.J., Prabhakar S., Binukumar B.K., Wani W.Y., Gupta N., Sharma D.R., Sunkaria A., Grover V.K., Bhardwaj N., Jain K., Gill K.D. Apo-Eepsilon4 allele in conjunction with Abeta42 and tau in CSF: biomarker for Alzheimer's disease. Curr. Alzheimer Res. 2011, 8:187-196.
142. Kandimalla R.J., Wani W.Y., Anand R., Kaushal A., Prabhakar S., Grover V.K., Bharadwaj N., Jain K., Gill K.D. Apolipoprotein E levels in the cerebrospinal fluid of north Indian patients with Alzheimer's disease. Am. J. Alzheimers Dis. Other Demen. 2013, 28:258-262.
143. Swerdlow R.H. Bioenergetic medicine. Br. J. Pharmacol. 2014, 171:1854-1869.
144. Swerdlow R.H., Khan S.M. A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease. Med. Hypotheses 2004, 63:8-20.
145. Swerdlow R.H., Khan S.M. The Alzheimer's disease mitochondrial cascade hypothesis: an update. Exp. Neurol. 2009, 218:308-315.
146. Reddy P.H., Manczak M., Mao P., Calkins M.J., Reddy A.P., Shirendeb U. Amyloid-beta and mitochondria in aging and Alzheimer's disease: implications for synaptic damage and cognitive decline. J. Alzheimers Dis. 2010, 20(Suppl. 2):S499-S512.
147. Lin M.T., Simon D.K., Ahn C.H., Kim L.M., Beal M.F. High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain. Hum. Mol. Genet. 2002, 11:133-145.
148. Coskun P.E., Beal M.F., Wallace D.C. Alzheimer's brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:10726-10731.
149. Coskun P.E., Wyrembak J., Derbereva O., Melkonian G., Doran E., Lott I.T., Head E., Cotman C.W., Wallace D.C. Systemic mitochondrial dysfunction and the etiology of Alzheimer's disease and down syndrome dementia. J. Alzheimers Dis. 2010, 20(Suppl. 2):S293-S310.
150. Lakatos A., Derbeneva O., Younes D., Keator D., Bakken T., Lvova M., Brandon M., Guffanti G., Reglodi D., Saykin A., Weiner M., Macciardi F., Schork N., Wallace D.C., Potkin S.G. Association between mitochondrial DNA variations and Alzheimer's disease in the ADNI cohort. Neurobiol. Aging 2010, 31:1355-1363.
151. Manczak M., Park B.S., Jung Y., Reddy P.H. Differential expression of oxidative phosphorylation genes in patients with Alzheimer's disease: implications for early mitochondrial dysfunction and oxidative damage. Neruomol. Med. 2004, 5:147-162.
152. Reddy P.H., McWeeney S., Park B.S., Manczak M., Gutala R.V., Partovi D., Jung Y., Yau V., Searles R., Mori M., Quinn J. Gene expression profiles of transcripts in amyloid precursor protein transgenic mice: up-regulation of mitochondrial metabolism and apoptotic genes is an early cellular change in Alzheimer's disease. Hum. Mol. Genet. 2004, 13:1225-1240.
153. Zhu X., Perry G., Smith M.A., Wang X. Abnormal mitochondrial dynamics in the pathogenesis of Alzheimer's disease. J. Alzheimers Dis. 2013, 33(Suppl. 1):S253-S262.
154. Silva D.F., Selfridge J.E., Lu J., Roy L.E.N., Hutfles L., Burns J.M., Michaelis E.K., Yan S., Cardoso S.M., Swerdlow R.H. Bioenergetic flux, mitochondrial mass and mitochondrial morphology dynamics in AD and MCI cybrid cell lines. Hum. Mol. Genet. 2013, 22:3931-3946.
155. Smith M.A., Perry G., Richey P.L., Sayre L.M., Anderson V.E., Beal M.F., Kowall N. Oxidative damage in Alzheimer's. Nature 1996, 382:120-121.
156. Maurer I., Zierz S., Moller H.J. A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients. Neurobiol. Aging 2000, 21:455-462.
157. Rosenberger A.F., Hilhorst R., Coart E., García Barrado L., Naji F., Rozemuller A.J., van der Flier W.M., Scheltens P., Hoozemans J.J., van der Vies S.M. Protein Kinase Activity Decreases with Higher Braak Stages of Alzheimer's Disease Pathology. J. Alzheimers. Dis. 2015, [Epub ahead of print] PubMed PMID: 26519433.
158. Devi L., Prabhu B.M., Galati D.F., Avadhani N.G., Anandatheerthavarada H.K. Accumulation of amyloid precursor protein in the mitochondrial import channels of human Alzheimer's disease brain is associated with mitochondrial dysfunction. J. Neurosci. 2006, 26:9057-9068.
159. Manczak M., Anekonda T.S., Henson E., Park B.S., Quinn J., Reddy P.H. Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum. Mol. Genet. 2006, 15:1437-1449.
160. Du H., Guo L., Fang F., Chen D., Sosunov A.A., McKhann G.M., Yan Y., Wang C., Zhang H., Molkentin J.D., Gunn-Moore F.J., Vonsattel J.P., Arancio O., Chen J.X., Yan S.D. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nat. Med. 2008, 14:1097-1105.
161. Lustbader J.W., Cirilli M., Lin C., Xu H.W., Takuma K., Wang N., Caspersen C., Chen X., Pollak S., Chaney M., Trinchese F., Liu S., Gunn-Moore F., Lue L.F., Walker D.G., Kuppusamy P., Zewier Z.L., Arancio O., Stern D., Yan S.S., Wu H. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease. Science 2004, 304:448-452.
162. Caspersen C., Wang N., Yao J., Sosunov A., Chen X., Lustbader J.W., Xu H.W., Stern D., McKhann G., Yan S.D. Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease. FASEB J. 2005, 19:2040-2041.
163. Eckert A., Hauptmann S., Scherping I., Rhein V., Muller-Spahn F., Gotz J., Muller W.E. Soluble beta-amyloid leads to mitochondrial defects in amyloid precursor protein and tau transgenic mice. Neurodegener. Dis. 2008, 5:157-159.
164. Rhein V., Baysang G., Rao S., Meier F., Bonert A., Muller-Spahn F., Eckert A. Amyloid-beta leads to impaired cellular respiration, energy production and mitochondrial electron chain complex activities in human neuroblastoma cells. Cell. Mol. Neurobiol. 2009, 29:1063-1071.
165. Drago D., Cavaliere A., Mascetra N., Ciavardelli D., di Ilio C., Zatta P., Sensi S.L. Aluminum modulates effects of beta amyloid(1-42) on neuronal calcium homeostasis and mitochondria functioning and is altered in a triple transgenic mouse model of Alzheimer's disease. Rejuvenation Res. 2008, 11:861-871.
166. Resende R., Moreira P.I., Proenca T., Deshpande A., Busciglio J., Pereira C., Oliveira C.R. Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease. Free Radic. Biol. Med. 2008, 44:2051-2057.
167. Sensi S.L., Rapposelli I.G., Frazzini V., Mascetra N. Altered oxidant-mediated intraneuronal zinc mobilization in a triple transgenic mouse model of Alzheimer's disease. Exp. Gerontol. 2008, 43:488-492.
168. Yao J., Irwin R.W., Zhao L., Nilsen J., Hamilton R.T., Brinton R.D. Mitochondrial bioenergetic deficit precedes Alzheimer's pathology in female mouse model of Alzheimer's disease. Proc. Natl. Acad. Sci. U. S. A. 2009, 106:14670-14675.
169. Dragicevic N., Mamcarz M., Zhu Y., Buzzeo R., Tan J., Arendash G.W., Bradshaw P.C. Mitochondrial amyloid-beta levels are associated with the extent of mitochondrial dysfunction in different brain regions and the degree of cognitive impairment in Alzheimer's transgenic mice. J. Alzheimers Dis. 2010, 20(Suppl. 2):S535-S550.
170. Pratico D., Uryu K., Leight S., Trojanoswki J.Q., Lee V.M. Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J. Neurosci. 2001, 21:4183-4187.
171. Calkins M.J., Reddy P.H. Assessment of newly synthesized mitochondrial DNA using BrdU labeling in primary neurons from Alzheimer's disease mice: implications for impaired mitochondrial biogenesis and synaptic damage. Biochim. Biophys. Acta 2011, 1812:1182-1189.
172. Crouch P.J., Blake R., Duce J.A., Ciccotosto G.D., Li Q.X., Barnham K.J., Curtain C.C., Cherny R.A., Cappai R., Dyrks T., Masters C.L., Trounce I.A. Copper-dependent inhibition of human cytochrome c oxidase by a dimeric conformer of amyloid-beta1-42. J. Neurosci. 2005, 25:672-679.
173. Hansson Petersen C.A., Alikhani N., Behbahani H., Wiehager B., Pavlov P.F., Alafuzoff I., Leinonen V., Ito A., Winblad B., Glaser E., Ankarcrona M. The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:13145-13150.
174. Devi L., Ohno M. Mitochondrial dysfunction and accumulation of the beta-secretase-cleaved C-terminal fragment of APP in Alzheimer's disease transgenic mice. Neurobiol. Dis. 2012, 45:417-424.
175. Amadoro G., Corsetti V., Ciotti M.T., Florenzano F., Capsoni S., Amato G., Calissano P. Endogenous Abeta causes cell death via early tau hyperphosphorylation. Neurobiol. Aging 2011, 32:969-990.
176. Atlante A., Amadoro G., Bobba A., de Bari L., Corsetti V., Pappalardo G., Marra E., Calissano P., Passarella S. A peptide containing residues 26-44 of tau protein impairs mitochondrial oxidative phosphorylation acting at the level of the adenine nucleotide translocator. Biochim. Biophys. Acta 2008, 1777:1289-1300.
177. Quintanilla R.A., Matthews-Roberson T.A., Dolan P.J., Johnson G.V. Caspase-cleaved tau expression induces mitochondrial dysfunction in immortalized cortical neurons: implications for the pathogenesis of Alzheimer disease. J. Biol. Chem. 2009, 284:18754-18766.
178. Wang X., Su B., Siedlak S.L., Moreira P.I., Fujioka H., Wang Y., Casadesus G., Zhu X. Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:19318-19323.
179. Nakanishi N., Ryan S.D., Zhang X., Khan A., Holland T., Cho E.G., Huang X., Liao F.F., Xu H., Lipton S.A., Tu S. Synaptic protein alpha1-takusan mitigates amyloid-beta-induced synaptic loss via interaction with tau and postsynaptic density-95 at postsynaptic sites. J. Neurosci. 2013, 33:14170-14183.
180. Koehler C.M. New developments in mitochondrial assembly. Annu. Rev. Cell Dev. Biol. 2004, 20:309-335.
181. Uren R.T., Dewson G., Bonzon C., Lithgow T., Newmeyer D.D., Kluck R.M. Mitochondrial release of pro-apoptotic proteins: electrostatic interactions can hold cytochrome c but not Smac/DIABLO to mitochondrial membranes. J. Biol. Chem. 2005, 280:2266-2274.
182. Parone P.A., Da Cruz S., Tondera D., Mattenberger Y., James D.I., Maechler P., Barja F., Martinou J.C. Preventing mitochondrial fission impairs mitochondrial function and leads to loss of mitochondrial DNA. PLoS One 2008, 3.
183. Arnoult D. Mitochondrial fragmentation in apoptosis. Trends Cell Biol. 2007, 17:6-12.
184. Cassidy-Stone A., Chipuk J.E., Ingerman E., Song C., Yoo C., Kuwana T., Kurth M.J., Shaw J.T., Hinshaw J.E., Green D.R., Nunnari J. Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev. Cell 2008, 14:193-204.
185. Chen H., Detmer S.A., Ewald A.J., Griffin E.E., Fraser S.E., Chan D.C. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J. Cell Biol. 2003, 160:189-200.
186. Alavi M.V., Bette S., Schimpf S., Schuettauf F., Schraermeyer U., Wehrl H.F., Ruttiger L., Beck S.C., Tonagel F., Pichler B.J., Knipper M., Peters T., Laufs J., Wissinger B. A splice site mutation in the murine Opa1 gene features pathology of autosomal dominant optic atrophy. Brain 2007, 130:1029-1042.
187. Davies V.J., Hollins A.J., Piechota M.J., Yip W., Davies J.R., White K.E., Nicols P.P., Boulton M.E., Votruba M. Opa1 deficiency in a mouse model of autosomal dominant optic atrophy impairs mitochondrial morphology, optic nerve structure and visual function. Hum. Mol. Genet. 2007, 16:1307-1318.
188. Verstreken P., Ly C.V., Venken K.J., Koh T.W., Zhou Y., Bellen H.J. Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions. Neuron 2005, 47:365-378.
189. Li H., Alavian K.N., Lazrove E., Mehta N., Jones A., Zhang P., Licznerski P., Graham M., Uo T., Guo J., Rahner C., Duman R.S., Morrison R.S., Jonas E.A. A Bcl-xL-Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis. Nat. Cell Biol. 2013, 15:773-785.
190. Molokanova E., Akhtar M.W., Sanz-Blasco S., Tu S., Pina-Crespo J.C., McKercher S.R., Lipton S.A. Differential effects of synaptic and extrasynaptic NMDA receptors on Abeta-induced nitric oxide production in cerebrocortical neurons. J. Neurosci. 2014, 34:5023-5028.
191. Cho D.H., Nakamura T., Fang J., Cieplak P., Godzik A., Gu Z., Lipton S.A. S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury. Science 2009, 324:102-105.
192. Qu J., Nakamura T., Cao G., Holland E.A., McKercher S.R., Lipton S.A. S-Nitrosylation activates Cdk5 and contributes to synaptic spine loss induced by beta-amyloid peptide. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:14330-14335.
193. Qu J., Nakamura T., Holland E.A., McKercher S.R., Lipton S.A. S-nitrosylation of Cdk5: potential implications in amyloid-beta-related neurotoxicity in Alzheimer disease. Prion 2012, 6:364-370.
194. Wang S., Song J., Tan M., Albers K.M., Jia J. Mitochondrial fission proteins in peripheral blood lymphocytes are potential biomarkers for Alzheimer's disease. Eur. J. Neurol. 2012, 19:1015-1022.
195. Swerdlow R.H., Burns J.M., Khan S.M. The Alzheimer's disease mitochondrial cascade hypothesis. J. Alzheimers Dis. 2010, 20(Suppl. 2):S265-S279.
196. Streck E.L., Czapski G.A., Goncalves da Silva C. Neurodegeneration, mitochondrial dysfunction, and oxidative stress. Oxidative Med. Cell. Longev. 2013, 2013:826046.
197. Morrison R.S., Kinoshita Y., Johnson M.D., Guo W., Garden G.A. p53-dependent cell death signaling in neurons. Neurochem. Res. 2003, 28:15-27.
198. Bae B.I., Xu H., Igarashi S., Fujimuro M., Agrawal N., Taya Y., Hayward S.D., Moran T.H., Montell C., Ross C.A., Snyder S.H., Sawa A. p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease. Neuron 2005, 47:29-41.
199. Silva A.R., Santos A.C., Farfel J.M., Grinberg L.T., Ferretti R.E., Campos A.H., Cunha I.W., Begnami M.D., Rocha R.M., Carraro D.M., de Braganca Pereira C.A., Jacob-Filho W., Brentani H. Repair of oxidative DNA damage, cell-cycle regulation and neuronal death may influence the clinical manifestation of Alzheimer's disease. PLoS One 2014, 9.
200. Manczak M., Reddy P.H. RNA silencing of genes involved in Alzheimer's disease enhances mitochondrial function and synaptic activity. Biochim. Biophys. Acta 2013, 1832:2368-2378.
201. Barsoum M.J., Yuan H., Gerencser A.A., Liot G., Kushnareva Y., Graber S., Kovacs I., Lee W.D., Waggoner J., Cui J., White A.D., Bossy B., Martinou J.C., Youle R.J., Lipton S.A., Ellisman M.H., Perkins G.A., Bossy-Wetzel E. Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons. EMBO J. 2006, 25:3900-3911.
202. Uo T., Kinoshita Y., Morrison R.S. Apoptotic actions of p53 require transcriptional activation of PUMA and do not involve a direct mitochondrial/cytoplasmic site of action in postnatal cortical neurons. J. Neurosci. 2007, 27:12198-12210.
203. Karbowski M., Lee Y.J., Gaume B., Jeong S.Y., Frank S., Nechushtan A., Santel A., Fuller M., Smith C.L., Youle R.J. Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis. J. Cell Biol. 2002, 159:931-938.
204. Wang D.B., Garden G.A., Kinoshita C., Wyles C., Babazadeh N., Sopher B., Kinoshita Y., Morrison R.S. Declines in Drp1 and parkin expression underlie DNA damage-induced changes in mitochondrial length and neuronal death. J. Neurosci. 2013, 33:1357-1365.
205. Guo X., Sesaki H., Qi X. Drp1 stabilizes p53 on the mitochondria to trigger necrosis under oxidative stress conditions in vitro and in vivo. Biochem. J. 2014, 461:137-146.
206. Maffioletti E., Tardito D., Gennarelli M., Bocchio-Chiavetto L. Micro spies from the brain to the periphery: new clues from studies on microRNAs in neuropsychiatric disorders. Front. Cell. Neurosci. 2014, 8:75.
207. Delay C., Hebert S.S. MicroRNAs and Alzheimer's disease mouse models: current insights and future research aAvenues. Int. J. Alzheimers Dis. 2011, 2011:894938.
208. Junn E., Mouradian M.M. MicroRNAs in neurodegenerative diseases and their therapeutic potential. Pharmacol. Ther. 2012, 133:142-150.
209. J. Nunez-Iglesias, C.C. Liu, T.E. Morgan, C.E. Finch, X.J. Zhou, Joint genome-wide profiling of miRNA and mRNA expression in Alzheimer's disease cortex reveals altered miRNA regulation, PLoS One 5 (185) e8898.
210. Schonrock N., Matamales M., Ittner L.M., Gotz J. MicroRNA networks surrounding APP and amyloid-beta metabolism-implications for Alzheimer's disease. Exp. Neurol. 2012, 235:447-454.
211. Wang J.X., Jiao J.Q., Li Q., Long B., Wang K., Liu J.P., Li Y.R., Li P.F. miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1. Nat. Med. 2011, 17:71-78.
212. Hebert S.S., Horre K., Nicolai L., Bergmans B., Papadopoulou A.S., Delacourte A., De Strooper B. MicroRNA regulation of Alzheimer's Amyloid precursor protein expression. Neurobiol. Dis. 2009, 33:422-428.
213. Patel N., Hoang D., Miller N., Ansaloni S., Huang Q., Rogers J.T., Lee J.C., Saunders A.J. MicroRNAs can regulate human APP levels. Mol. Neurodegener. 2008, 3:10.
214. Wang T., Chen K., Li H., Dong S., Su N., Liu Y., Cheng Y., Dai J., Yang C., Xiao S. The feasibility of utilizing plasma miRNA107 and BACE1 messenger RNA gene expression for clinical diagnosis of amnestic mild cognitive impairment. J. Clin. Psychiatry 2015, 76:135-141.
215. Li J., Donath S., Li Y., Qin D., Prabhakar B.S., Li P. miR-30 regulates mitochondrial fission through targeting p53 and the dynamin-related protein-1 pathway. PLoS Genet. 2010, 6.
216. Han X.J., Lu Y.F., Li S.A., Kaitsuka T., Sato Y., Tomizawa K., Nairn A.C., Takei K., Matsui H., Matsushita M. CaM kinase I alpha-induced phosphorylation of Drp1 regulates mitochondrial morphology. J. Cell Biol. 2008, 182:573-585.