Mitochondria-derived damage-associated molecular patterns in neurodegeneration

Frontiers in Immunology

Volumn 8, Issue APR, 2017, Pages

  Wilkins, Heather M ^a,b   Weidling, Ian W ^a,b   Ji, Yan ^a,b   Swerdlow, Russell H ^a,b  

^a UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

Author keywords

Damage associated molecular pattern; Mitochondria; Neurodegeneration; Neuroinflammation; Sterile inflammation

Indexed keywords

CELL PROTEIN; MITOCHONDRIA DERIVED DAMAGE ASSOCIATED MOLECULAR PATTERN; MITOCHONDRIAL DNA; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; CELL FUNCTION; CELL ORGANELLE; CLINICAL TRIAL (TOPIC); DISORDERS OF MITOCHONDRIAL FUNCTIONS; HUMAN; INFLAMMATION; MITOCHONDRION; NERVE DEGENERATION; NONHUMAN; PARKINSON DISEASE; PROTEIN SECRETION; REVIEW;

EID: 85018421245     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2017.00508     Document Type: Review

References (184)

1. Oka T, Hikoso S, Yamaguchi O, Taneike M, Takeda T, Tamai T, et al. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature (2012) 485(7397):251-5. doi: 10.1038/nature10992
2. Lam NY, Rainer TH, Chiu RW, Joynt GM, Lo YM. Plasma mitochondrial DNA concentrations after trauma. Clin Chem (2004) 50(1):213-6. doi:10.1373/clinchem.2003.025783
3. Walko TD III, Bola RA, Hong JD, Au AK, Bell MJ, Kochanek PM, et al. Cerebrospinal fluid mitochondrial DNA: a novel DAMP in pediatric traumatic brain injury. Shock (2014) 41(6):499-503. doi:10.1097/SHK.0000000000000160
4. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature (2010) 464(7285):104-7. doi:10.1038/nature08780
5. Collins LV, Hajizadeh S, Holme E, Jonsson IM, Tarkowski A. Endogenously oxidized mitochondrial DNA induces in vivo and in vitro inflammatory responses. J Leukoc Biol (2004) 75(6):995-1000. doi:10.1189/jlb.0703328
6. Di Filippo M, Chiasserini D, Tozzi A, Picconi B, Calabresi P. Mitochondria and the link between neuroinflammation and neurodegeneration. J Alzheimers Dis (2010) 20(Suppl 2):S369-79. doi:10.3233/JAD-2010-100543
7. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell (2010) 140(6):918-34. doi:10.1016/j.cell.2010.02.016
8. Hensley K. Neuroinflammation in Alzheimer's disease: mechanisms, pathologic consequences, and potential for therapeutic manipulation. J Alzheimers Dis (2010) 21(1):1-14. doi:10.3233/JAD-2010-1414
9. Mathew A, Lindsley TA, Sheridan A, Bhoiwala DL, Hushmendy SF, Yager EJ, et al. Degraded mitochondrial DNA is a newly identified subtype of the damage associated molecular pattern (DAMP) family and possible trigger of neurodegeneration. J Alzheimers Dis (2012) 30(3):617-27. doi:10.3233/JAD-2012-120145
10. Abramova NE, Davies KJ, Crawford DR. Polynucleotide degradation during early stage response to oxidative stress is specific to mitochondria. Free Radic Biol Med (2000) 28(2):281-8. doi:10.1016/S0891-5849(99)00239-7
11. in 't Veld BA, Ruitenberg A, Hofman A, Launer LJ, van Duijn CM, Stijnen T, et al. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. N Engl J Med (2001) 345(21):1515-21. doi:10.1056/NEJMoa010178
12. Stewart WF, Kawas C, Corrada M, Metter EJ. Risk of Alzheimer's disease and duration of NSAID use. Neurology (1997) 48(3):626-32. doi:10.1212/WNL.48.3.626
13. Szekely CA, Breitner JC, Fitzpatrick AL, Rea TD, Psaty BM, Kuller LH, et al. NSAID use and dementia risk in the Cardiovascular Health Study: role of APOE and NSAID type. Neurology (2008) 70(1):17-24. doi:10.1212/01.wnl.0000284596.95156.48
14. Cornelius C, Fastbom J, Winblad B, Viitanen M. Aspirin, NSAIDs, risk of dementia, and influence of the apolipoprotein E epsilon 4 allele in an elderly population. Neuroepidemiology (2004) 23(3):135-43. doi:10.1159/000075957
15. Vlad SC, Miller DR, Kowall NW, Felson DT. Protective effects of NSAIDs on the development of Alzheimer disease. Neurology (2008) 70(19):1672-7. doi:10.1212/01.wnl.0000311269.57716.63
16. Rogers J, Kirby LC, Hempelman SR, Berry DL, McGeer PL, Kaszniak AW, et al. Clinical trial of indomethacin in Alzheimer's disease. Neurology (1993) 43(8):1609-11. doi:10.1212/WNL.43.8.1609
17. Scharf S, Mander A, Ugoni A, Vajda F, Christophidis N. A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer's disease. Neurology (1999) 53(1):197-201. doi:10.1212/WNL.53.1.197
18. Wilcock GK, Black SE, Hendrix SB, Zavitz KH, Swabb EA, Laughlin MA, et al. Efficacy and safety of tarenflurbil in mild to moderate Alzheimer's disease: a randomised phase II trial. Lancet Neurol (2008) 7(6):483-93. doi:10.1016/s1474-4422(08)70090-5
19. Daniels MJD, Rivers-Auty J, Schilling T, Spencer NG, Watremez W, Fasolino V, et al. Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer's disease in rodent models. Nat Commun (2016) 7:12504. doi:10.1038/ncomms12504
20. Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, et al. TREM2 variants in Alzheimer's disease. N Engl J Med (2012) 368(2):117-27. doi:10.1056/NEJMoa1211851
21. Wang Y, Cella M, Mallinson K, Ulrich JD, Young KL, Robinette ML, et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model. Cell (2015) 160(6):1061-71. doi:10.1016/j.cell.2015.01.049
22. Kleinberger G, Yamanishi Y, Suarez-Calvet M, Czirr E, Lohmann E, Cuyvers E, et al. TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Sci Transl Med (2014) 6(243):243ra86. doi:10.1126/scitranslmed.3009093
23. Gispert JD, Suarez-Calvet M, Monte GC, Tucholka A, Falcon C, Rojas S, et al. Cerebrospinal fluid sTREM2 levels are associated with gray matter volume increases and reduced diffusivity in early Alzheimer's disease. Alzheimers Dement (2016) 12(12):1259-72. doi:10.1016/j.jalz.2016.06.005
24. Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML, et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet (2009) 41(10):1088-93. doi:10.1038/ng.440
25. Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M, et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nat Genet (2009) 41(10):1094-9. doi:10.1038/ng.439
26. McGeer PL, McGeer EG. Polymorphisms in inflammatory genes and the risk of Alzheimer disease. Arch Neurol (2001) 58(11):1790-2. doi:10.1001/archneur.58.11.1790
27. Hazrati LN, Van Cauwenberghe C, Brooks PL, Brouwers N, Ghani M, Sato C, et al. Genetic association of CR1 with Alzheimer's disease: a tentative disease mechanism. Neurobiol Aging (2012) 33(12): 2949.e5-12. doi:10.1016/j.neurobiolaging.2012.07.001
28. Hollingworth P, Harold D, Sims R, Gerrish A, Lambert JC, Carrasquillo MM, et al. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nat Genet (2011) 43(5):429-35. doi:10.1038/ng.803
29. Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nat Genet (2013) 45(12):1452-8. doi:10.1038/ng.2802
30. Wilkins HM, Carl SM, Greenlief AC, Festoff BW, Swerdlow RH. Bioenergetic dysfunction and inflammation in Alzheimer's disease: a possible connection. Front Aging Neurosci (2014) 6:311. doi:10.3389/fnagi.2014.00311
31. Perlmutter LS, Barron E, Chui HC. Morphologic association between microglia and senile plaque amyloid in Alzheimer's disease. Neurosci Lett (1990) 119(1):32-6. doi:10.1016/0304-3940(90)90748-X
32. Medeiros R, LaFerla FM. Astrocytes: conductors of the Alzheimer disease neuroinflammatory symphony. Exp Neurol (2013) 239:133-8. doi:10.1016/j.expneurol.2012.10.007
33. Griffin WS, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, et al. Brain interleukin 1 and S-100 immunoreactivity are elevated in down syndrome and Alzheimer disease. Proc Natl Acad Sci U S A (1989) 86(19):7611-5. doi:10.1073/pnas.86.19.7611
34. Sheng JG, Mrak RE, Griffin WST. Microglial inter leukin-1a expression in brain regions in Alzheimer's disease: correlation with neuritic plaque distribution. Neuropathol Appl Neurobiol (1995) 21(4):290-301. doi:10.1111/j.1365-2990.1995.tb01063.x
35. Laske C, Stransky E, Hoffmann N, Maetzler W, Straten G, Eschweiler GW, et al. Macrophage colony-stimulating factor (M-CSF) in plasma and CSF of patients with mild cognitive impairment and Alzheimer's disease. Curr Alzheimer Res (2010) 7(5):409-14. doi:10.2174/156720510791383813
36. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, et al. Inflammation and Alzheimer's disease. Neurobiol Aging (2000) 21(3):383-421. doi:10.1016/S0197-4580(00)00124-X
37. McGeer PL, Itagaki S, Boyes BE, McGeer EG. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains. Neurology (1988) 38(8):1285-91. doi:10.1212/WNL.38.8.1285
38. Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease. Neurobiol Dis (2006) 21(2):404-12. doi:10.1016/j.nbd.2005.08.002
39. Hunot S, Dugas N, Faucheux B, Hartmann A, Tardieu M, Debre P, et al. FcepsilonRII/CD23 is expressed in Parkinson's disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells. J Neurosci (1999) 19(9):3440-7
40. Barcia C, Ros CM, Ros-Bernal F, Gómez A, Annese V, Carrillo-de Sauvage MA, et al. Persistent phagocytic characteristics of microglia in the substantia nigra of long-term parkinsonian macaques. J Neuroimmunol (2013) 261(1-2):60-6. doi:10.1016/j.jneuroim.2013.05.001
41. Song YJC, Halliday GM, Holton JL, Lashley T, Sullivan SS, McCann H, et al. Degeneration in different parkinsonian syndromes relates to astrocyte type and astrocyte protein expression. J Neuropathol Exp Neurol (2009) 68(10):1073. doi:10.1097/NEN.0b013e3181b66f1b
42. Tong J, Ang L-C, Williams B, Furukawa Y, Fitzmaurice P, Guttman M, et al. Low levels of astroglial markers in Parkinson's disease: relationship to a-synuclein accumulation. Neurobiol Dis (2015) 82:243-53. doi:10.1016/j.nbd.2015.06.010
43. Wahner AD, Bronstein JM, Bordelon YM, Ritz B. Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease. Neurology (2007) 69(19):1836-42. doi:10.1212/01.wnl.0000279519.99344.ad
44. Klein C, Westenberger A. Genetics of Parkinson's disease. Cold Spring Harb Perspect Med (2012) 2(1):a008888. doi:10.1101/cshperspect.a008888
45. Ma B, Xu L, Pan X, Sun L, Ding J, Xie C, et al. LRRK2 modulates microglial activity through regulation of chemokine (C-X3-C) receptor 1-mediated signalling pathways. Hum Mol Genet (2016) 25(16):3515-23. doi:10.1093/hmg/ddw194
46. Russo I, Bubacco L, Greggio E. LRRK2 and neuroinflammation: partners in crime in Parkinson's disease? J Neuroinflammation (2014) 11:52. doi:10.1186/1742-2094-11-52
47. Choi I, Kim B, Byun JW, Baik SH, Huh YH, Kim JH, et al. LRRK2 G2019S mutation attenuates microglial motility by inhibiting focal adhesion kinase. Nat Commun (2015) 6:8255. doi:10.1038/ncomms9255
48. Baba Y, Kuroiwa A, Uitti RJ, Wszolek ZK, Yamada T. Alterations of T-lymphocyte populations in Parkinson disease. Parkinsonism Relat Disord (2005) 11(8):493-8. doi:10.1016/j.parkreldis.2005.07.005
49. Kortekaas R, Leenders KL, van Oostrom JC, Vaalburg W, Bart J, Willemsen AT, et al. Blood-brain barrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol (2005) 57(2):176-9. doi:10.1002/ana.20369
50. Chen H, O'Reilly EJ, Schwarzschild MA, Ascherio A. Peripheral inflammatory biomarkers and risk of Parkinson's disease. Am J Epidemiol (2008) 167(1):90-5. doi:10.1093/aje/kwm260
51. Brochard V, Combadiere B, Prigent A, Laouar Y, Perrin A, Beray-Berthat V, et al. Infiltration of CD4+ lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease. J Clin Invest (2009) 119(1):182-92. doi:10.1172/jci36470
52. Donnenfeld H, Kascsak RJ, Bartfeld H. Deposits of IgG and C3 in the spinal cord and motor cortex of ALS patients. J Neuroimmunol (1984) 6(1):51-7. doi:10.1016/0165-5728(84)90042-0
53. Lampson LA, Kushner PD, Sobel RA. Major histocompatibility complex antigen expression in the affected tissues in amyotrophic lateral sclerosis. Ann Neurol (1990) 28(3):365-72. doi:10.1002/ana.410280311
54. Troost D, Van den Oord JJ, Vianney de Jong JM. Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol (1990) 16(5):401-10. doi:10.1111/j.1365-2990.1990.tb01276.x
55. Kawamata T, Akiyama H, Yamada T, McGeer PL. Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am J Pathol (1992) 140(3):691-707
56. Turner MR, Cagnin A, Turkheimer FE, Miller CCJ, Shaw CE, Brooks DJ, et al. Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol Dis (2004) 15(3):601-9. doi:10.1016/j.nbd.2003.12.012
57. Schiffer D, Cordera S, Cavalla P, Migheli A. Reactive astrogliosis of the spinal cord in amyotrophic lateral sclerosis. J Neurol Sci (1996) 139(Suppl):27-33. doi:10.1016/0022-510X(96)00073-1
58. Boillee S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA, Kassiotis G, et al. Onset and progression in inherited ALS determined by motor neurons and microglia. Science (2006) 312(5778):1389-92. doi:10.1126/science.1123511
59. Yamanaka K, Chun SJ, Boillee S, Fujimori-Tonou N, Yamashita H, Gutmann DH, et al. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat Neurosci (2008) 11(3):251-3. doi:10.1038/nn2047
60. Lopez-Lopez A, Gamez J, Syriani E, Morales M, Salvado M, Rodriguez MJ, et al. CX3CR1 is a modifying gene of survival and progression in amyotrophic lateral sclerosis. PLoS One (2014) 9(5):e96528. doi:10.1371/journal.pone.0096528
61. Wolf Y, Yona S, Kim KW, Jung S. Microglia, seen from the CX3CR1 angle. Front Cell Neurosci (2013) 7:26. doi:10.3389/fncel.2013.00026
62. Brohawn DG, O'Brien LC, Bennett JP Jr. RNAseq analyses identify tumor necrosis factor-mediated inflammation as a major abnormality in ALS spinal cord. PLoS One (2016) 11(8):e0160520. doi:10.1371/journal.pone.0160520
63. Lu C, Cortopassi G. Frataxin knockdown causes loss of cytoplasmic iron-sulfur cluster functions, redox alterations and induction of heme transcripts. Arch Biochem Biophys (2007) 457(1):111-22. doi:10.1016/j.abb.2006.09.010
64. Hayashi G, Cortopassi G. Oxidative stress in inherited mitochondrial diseases. Free Radic Biol Med (2015) 88(Pt A):10-7. doi:10.1016/j.freeradbiomed.2015.05.039
65. Kaplan J. Friedreich's ataxia is a mitochondrial disorder. Proc Natl Acad Sci U S A (1999) 96(20):10948-9. doi:10.1073/pnas.96.20.10948
66. Hayashi G, Shen Y, Pedersen TL, Newman JW, Pook M, Cortopassi G. Frataxin deficiency increases cyclooxygenase 2 and prostaglandins in cell and animal models of Friedreich's ataxia. Hum Mol Genet (2014) 23(25):6838-47. doi:10.1093/hmg/ddu407
67. Makino M, Horai S, Goto Y, Nonaka I. Mitochondrial DNA mutations in Leigh syndrome and their phylogenetic implications. J Hum Genet (2000) 45(2):69-75. doi:10.1007/s100380050014
68. Thorburn DR, Rahman S. Mitochondrial DNA-associated Leigh syndrome and NARP. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al., editors. GeneReviews(R). Seattle, WA (1993)
69. Johnson SC, Yanos ME, Kayser EB, Quintana A, Sangesland M, Castanza A, et al. mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Science (2013) 342(6165):1524-8. doi:10.1126/science.1244360
70. Bull PC, Thomas GR, Rommens JM, Forbes JR, Cox DW. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nat Genet (1993) 5(4):327-37. doi:10.1038/ng1293-327
71. Das SK, Ray K. Wilson's disease: an update. Nat Clin Pract Neurol (2006) 2(9):482-93. doi:10.1038/ncpneuro0291
72. Lutsenko S, Cooper MJ. Localization of the Wilson's disease protein product to mitochondria. Proc Natl Acad Sci U S A (1998) 95(11):6004-9. doi:10.1073/pnas.95.11.6004
73. Gu M, Cooper JM, Butler P, Walker AP, Mistry PK, Dooley JS, et al. Oxidative-phosphorylation defects in liver of patients with Wilson's disease. Lancet (2000) 356(9228):469-74. doi:10.1016/S0140-6736(00)02556-3
74. Rossi L, Lombardo MF, Ciriolo MR, Rotilio G. Mitochondrial dysfunction in neurodegenerative diseases associated with copper imbalance. Neurochem Res (2004) 29(3):493-504. doi:10.1023/B:NERE.0000014820.99232.8a
75. Wang H, Cheng N, Dong J, Wang X, Han Y, Yang R, et al. Serum pentraxin 3 is elevated in patients with neurological Wilson's disease. Clin Chim Acta (2016) 462:178-82. doi:10.1016/j.cca.2016.08.010
76. Scheffler IE. A century of mitochondrial research: achievements and perspectives. Mitochondrion (2001) 1(1):3-31. doi:10.1016/S1567-7249(00)00002-7
77. Swerdlow RH. Mitochondrial medicine and the neurodegenerative mitochondriopathies. Pharmaceuticals (Basel) (2009) 2(3):150-67. doi:10.3390/ph2030150
78. Swerdlow RH. Mitochondria and cell bioenergetics: increasingly recognized components and a possible etiologic cause of Alzheimer's disease. Antioxid Redox Signal (2012) 16(12):1434-55. doi:10.1089/ars.2011.4149
79. Lezi E, Swerdlow RH. Mitochondria in neurodegeneration. Adv Exp Med Biol (2012) 942:269-86. doi:10.1007/978-94-007-2869-1_12
80. Beal MF. Mitochondria take center stage in aging and neurodegeneration. Ann Neurol (2005) 58(4):495-505. doi:10.1002/ana.20624
81. Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature (2006) 443(7113):787-95. doi:10.1038/nature05292
82. Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, et al. Mitochondrial abnormalities in Alzheimer's disease. J Neurosci (2001) 21(9):3017-23
83. Parker WD Jr, Filley CM, Parks JK. Cytochrome oxidase deficiency in Alzheimer's disease. Neurology (1990) 40(8):1302-3. doi:10.1212/WNL.40.8.1302
84. Parker WD Jr, Parks JK. Cytochrome c oxidase in Alzheimer's disease brain: purification and characterization. Neurology (1995) 45(3 Pt 1):482-6. doi:10.1212/WNL.45.3.482
85. Kish SJ. Brain energy metabolizing enzymes in Alzheimer's disease: alpha-ketoglutarate dehydrogenase complex and cytochrome oxidase. Ann N Y Acad Sci (1997) 826:218-28. doi:10.1111/j.1749-6632.1997.tb48473.x
86. Mutisya EM, Bowling AC, Beal MF. Cortical cytochrome oxidase activity is reduced in Alzheimer's disease. J Neurochem (1994) 63(6):2179-84. doi:10.1046/j.1471-4159.1994.63062179.x
87. Cardoso SM, Proenca MT, Santos S, Santana I, Oliveira CR. Cytochrome c oxidase is decreased in Alzheimer's disease platelets. Neurobiol Aging (2004) 25(1):105-10. doi:10.1016/S0197-4580(03)00033-2
88. Curti D, Rognoni F, Gasparini L, Cattaneo A, Paolillo M, Racchi M, et al. Oxidative metabolism in cultured fibroblasts derived from sporadic Alzheimer's disease (AD) patients. Neurosci Lett (1997) 236(1):13-6. doi:10.1016/S0304-3940(97)00741-6
89. Mancuso M, Filosto M, Bosetti F, Ceravolo R, Rocchi A, Tognoni G, et al. Decreased platelet cytochrome c oxidase activity is accompanied by increased blood lactate concentration during exercise in patients with Alzheimer disease. Exp Neurol (2003) 182(2):421-6. doi:10.1016/S0014-4886(03)00092-X
90. Wilkins HM, Carl SM, Swerdlow RH. Cytoplasmic hybrid (cybrid) cell lines as a practical model for mitochondriopathies. Redox Biol (2014) 2:619-31. doi:10.1016/j.redox.2014.03.006
91. Khan SM, Cassarino DS, Abramova NN, Keeney PM, Borland MK, Trimmer PA, et al. Alzheimer's disease cybrids replicate beta-amyloid abnormalities through cell death pathways. Ann Neurol (2000) 48(2):148-55. doi:10.1002/1531-8249(200008)48:2<148::AID-ANA3>3.0.CO;2-7
92. Chang SW, Zhang D, Chung HD, Zassenhaus HP. The frequency of point mutations in mitochondrial DNA is elevated in the Alzheimer's brain. Biochem Biophys Res Commun (2000) 273(1):203-8. doi:10.1006/bbrc.2000.2885
93. Hamblet NS, Castora FJ. Elevated levels of the Kearns-Sayre syndrome mitochondrial DNA deletion in temporal cortex of Alzheimer's patients. Mutat Res (1997) 379(2):253-62. doi:10.1016/S0027-5107(97)00158-9
94. Krishnan KJ, Ratnaike TE, De Gruyter HL, Jaros E, Turnbull DM. Mitochondrial DNA deletions cause the biochemical defect observed in Alzheimer's disease. Neurobiol Aging (2012) 33(9):2210-4. doi:10.1016/j.neurobiolaging.2011.08.009
95. Lovell MA, Markesbery WR. Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer's disease. Nucleic Acids Res (2007) 35(22):7497-504. doi:10.1093/nar/gkm821
96. Mecocci P, MacGarvey U, Beal MF. Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease. Ann Neurol (1994) 36(5):747-51. doi:10.1002/ana.410360510
97. Phillips NR, Simpkins JW, Roby RK. Mitochondrial DNA deletions in Alzheimer's brains: a review. Alzheimers Dement (2014) 10(3):393-400. doi:10.1016/j.jalz.2013.04.508
98. Mosconi L, Berti V, Swerdlow RH, Pupi A, Duara R, de Leon M. Maternal transmission of Alzheimer's disease: prodromal metabolic phenotype and the search for genes. Hum Genomics (2010) 4(3):170-93. doi:10.1186/1479-7364-4-3-170
99. Mosconi L, Brys M, Switalski R, Mistur R, Glodzik L, Pirraglia E, et al. Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism. Proc Natl Acad Sci U S A (2007) 104(48):19067-72. doi:10.1073/pnas.0705036104
100. Mosconi L, de Leon M, Murray J, Lezi E, Lu J, Javier E, et al. Reduced mitochondria cytochrome oxidase activity in adult children of mothers with Alzheimer's disease. J Alzheimers Dis (2011) 27(3):483-90. doi:10.3233/JAD-2011-110866
101. Honea RA, Vidoni ED, Swerdlow RH, Burns JM; Alzheimer's Disease Neuroimaging Initiative. Maternal family history is associated with Alzheimer's disease biomarkers. J Alzheimers Dis (2012) 31(3):659-68. doi:10.3233/JAD-2012-120676
102. Edland SD, Silverman JM, Peskind ER, Tsuang D, Wijsman E, Morris JC. Increased risk of dementia in mothers of Alzheimer's disease cases: evidence for maternal inheritance. Neurology (1996) 47(1):254-6. doi:10.1212/WNL.47.1.254
103. Andrawis JP, Hwang KS, Green AE, Kotlerman J, Elashoff D, Morra JH, et al. Effects of ApoE4 and maternal history of dementia on hippocampal atrophy. Neurobiol Aging (2012) 33(5):856-66. doi:10.1016/j.neurobiolaging.2010.07.020
104. Fesahat F, Houshmand M, Panahi MS, Gharagozli K, Mirzajani F. Do haplogroups H and U act to increase the penetrance of Alzheimer's disease? Cell Mol Neurobiol (2007) 27(3):329-34. doi:10.1007/s10571-006-9126-9
105. Lakatos A, Derbeneva O, Younes D, Keator D, Bakken T, Lvova M, et al. Association between mitochondrial DNA variations and Alzheimer's disease in the ADNI cohort. Neurobiol Aging (2010) 31(8):1355-63. doi:10.1016/j.neurobiolaging.2010.04.031
106. Maruszak A, Canter JA, Styczynska M, Zekanowski C, Barcikowska M. Mitochondrial haplogroup H and Alzheimer's disease-is there a connection? Neurobiol Aging (2009) 30(11):1749-55. doi:10.1016/j.neurobiolaging.2008.01.004
107. Sian J, Youdim MBH, Riederer P, Gerlach M. MPTP-induced parkinsonian syndrome. In: Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD, editors. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th ed. Philadelphia: Lippincott-Raven (1999). Available from: https://www.ncbi.nlm.nih.gov/books/NBK27974/
108. Meredith GE, Rademacher DJ. MPTP mouse models of Parkinson's disease: an update. J Parkinsons Dis (2011) 1(1):19-33. doi:10.3233/JPD-2011-11023
109. Porras G, Li Q, Bezard E. Modeling Parkinson's disease in primates: the MPTP model. Cold Spring Harb Perspect Med (2012) 2(3):a009308. doi:10.1101/cshperspect.a009308
110. Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD. Mitochondrial complex I deficiency in Parkinson's disease. J Neurochem (1990) 54(3):823-7. doi:10.1111/j.1471-4159.1990.tb02325.x
111. Yoshino H, Nakagawa-Hattori Y, Kondo T, Mizuno Y. Mitochondrial complex I and II activities of lymphocytes and platelets in Parkinson's disease. J Neural Transm Park Dis Dement Sect (1992) 4(1):27-34. doi:10.1007/BF02257619
112. Haas RH, Nasirian F, Nakano K, Ward D, Pay M, Hill R, et al. Low platelet mitochondrial complex I and complex II/III activity in early untreated Parkinson's disease. Ann Neurol (1995) 37(6):714-22. doi:10.1002/ana.410370604
113. Keeney PM, Xie J, Capaldi RA, Bennett JP Jr. Parkinson's disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci (2006) 26(19):5256-64. doi:10.1523/JNEUROSCI.0984-06.2006
114. Swerdlow RH, Parks JK, Miller SW, Tuttle JB, Trimmer PA, Sheehan JP, et al. Origin and functional consequences of the complex I defect in Parkinson's disease. Ann Neurol (1996) 40(4):663-71. doi:10.1002/ana.410400417
115. Esteves AR, Domingues AF, Ferreira IL, Januario C, Swerdlow RH, Oliveira CR, et al. Mitochondrial function in Parkinson's disease cybrids containing an nt2 neuron-like nuclear background. Mitochondrion (2008) 8(3):219-28. doi:10.1016/j.mito.2008.03.004
116. Autere J, Moilanen JS, Finnila S, Soininen H, Mannermaa A, Hartikainen P, et al. Mitochondrial DNA polymorphisms as risk factors for Parkinson's disease and Parkinson's disease dementia. Hum Genet (2004) 115(1):29-35. doi:10.1007/s00439-004-1123-9
117. Ghezzi D, Marelli C, Achilli A, Goldwurm S, Pezzoli G, Barone P, et al. Mitochondrial DNA haplogroup K is associated with a lower risk of Parkinson's disease in Italians. Eur J Hum Genet (2005) 13(6):748-52. doi:10.1038/sj.ejhg.5201425
118. Pyle A, Foltynie T, Tiangyou W, Lambert C, Keers SM, Allcock LM, et al. Mitochondrial DNA haplogroup cluster UKJT reduces the risk of PD. Ann Neurol (2005) 57(4):564-7. doi:10.1002/ana.20417
119. Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, et al. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet (2006) 38(5):515-7. doi:10.1038/ng1769
120. Lin MT, Cantuti-Castelvetri I, Zheng K, Jackson KE, Tan YB, Arzberger T, et al. Somatic mitochondrial DNA mutations in early Parkinson and incidental Lewy body disease. Ann Neurol (2012) 71(6):850-4. doi:10.1002/ana.23568
121. Parker WD Jr, Parks JK. Mitochondrial ND5 mutations in idiopathic Parkinson's disease. Biochem Biophys Res Commun (2005) 326(3):667-9. doi:10.1016/j.bbrc.2004.11.093
122. Luoma PT, Eerola J, Ahola S, Hakonen AH, Hellstrom O, Kivisto KT, et al. Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease. Neurology (2007) 69(11):1152-9. doi:10.1212/01.wnl.0000276955.23735.eb
123. Dhaliwal GK, Grewal RP. Mitochondrial DNA deletion mutation levels are elevated in ALS brains. Neuroreport (2000) 11(11):2507-9. doi:10.1097/00001756-200008030-00032
124. Sasaki S, Horie Y, Iwata M. Mitochondrial alterations in dorsal root ganglion cells in sporadic amyotrophic lateral sclerosis. Acta Neuropathol (2007) 114(6):633-9. doi:10.1007/s00401-007-0299-1
125. Sasaki S, Iwata M. Mitochondrial alterations in the spinal cord of patients with sporadic amyotrophic lateral sclerosis. J Neuropathol Exp Neurol (2007) 66(1):10-6. doi:10.1097/nen.0b013e31802c396b
126. Borthwick GM, Johnson MA, Ince PG, Shaw PJ, Turnbull DM. Mitochondrial enzyme activity in amyotrophic lateral sclerosis: implications for the role of mitochondria in neuronal cell death. Ann Neurol (1999) 46(5):787-90. doi:10.1002/1531-8249(199911)46:5<787::AID-ANA17>3.0.CO;2-8
127. Wiedemann FR, Manfredi G, Mawrin C, Beal MF, Schon EA. Mitochondrial DNA and respiratory chain function in spinal cords of ALS patients. J Neurochem (2002) 80(4):616-25. doi:10.1046/j.0022-3042.2001.00731.x
128. Mawrin C, Kirches E, Krause G, Wiedemann FR, Vorwerk CK, Bogerts B, et al. Single-cell analysis of mtDNA deletion levels in sporadic amyotrophic lateral sclerosis. Neuroreport (2004) 15(6):939-43. doi:10.1097/00001756-200404290-00002
129. Crugnola V, Lamperti C, Lucchini V, Ronchi D, Peverelli L, Prelle A, et al. Mitochondrial respiratory chain dysfunction in muscle from patients with amyotrophic lateral sclerosis. Arch Neurol (2010) 67(7):849-54. doi:10.1001/archneurol.2010.128
130. Siklos L, Engelhardt J, Harati Y, Smith RG, Joo F, Appel SH. Ultrastructural evidence for altered calcium in motor nerve terminals in amyotropic lateral sclerosis. Ann Neurol (1996) 39(2):203-16. doi:10.1002/ana.410390210
131. Vielhaber S, Kunz D, Winkler K, Wiedemann FR, Kirches E, Feistner H, et al. Mitochondrial DNA abnormalities in skeletal muscle of patients with sporadic amyotrophic lateral sclerosis. Brain (2000) 123(Pt 7):1339-48. doi:10.1093/brain/123.7.1339
132. Curti D, Malaspina A, Facchetti G, Camana C, Mazzini L, Tosca P, et al. Amyotrophic lateral sclerosis: oxidative energy metabolism and calcium homeostasis in peripheral blood lymphocytes. Neurology (1996) 47(4):1060-4. doi:10.1212/WNL.47.4.1060
133. Nakano Y, Hirayama K, Terao K. Hepatic ultrastructural changes and liver dysfunction in amyotrophic lateral sclerosis. Arch Neurol (1987) 44(1):103-6. doi:10.1001/archneur.1987.00520130079022
134. Shrivastava M, Das TK, Behari M, Pati U, Vivekanandhan S. Ultrastructural variations in platelets and platelet mitochondria: a novel feature in amyotrophic lateral sclerosis. Ultrastruct Pathol (2011) 35(2):52-9. doi:10.3109/01913123.2010.541985
135. Shrivastava M, Vivekanandhan S, Pati U, Behari M, Das TK. Mitochondrial perturbance and execution of apoptosis in platelet mitochondria of patients with amyotrophic lateral sclerosis. Int J Neurosci (2011) 121(3):149-58. doi:10.3109/00207454.2010.537416
136. Swerdlow RH, Parks JK, Cassarino DS, Trimmer PA, Miller SW, Maguire DJ, et al. Mitochondria in sporadic amyotrophic lateral sclerosis. Exp Neurol (1998) 153(1):135-42. doi:10.1006/exnr.1998.6866
137. Mancuso M, Conforti FL, Rocchi A, Tessitore A, Muglia M, Tedeschi G, et al. Could mitochondrial haplogroups play a role in sporadic amyotrophic lateral sclerosis? Neurosci Lett (2004) 371(2-3):158-62. doi:10.1016/j.neulet.2004.08.060
138. Gurung P, Lukens JR, Kanneganti TD. Mitochondria: diversity in the regulation of the NLRP3 inflammasome. Trends Mol Med (2015) 21(3):193-201. doi:10.1016/j.molmed.2014.11.008
139. Heid ME, Keyel PA, Kamga C, Shiva S, Watkins SC, Salter RD. Mitochondrial reactive oxygen species induces NLRP3-dependent lysosomal damage and inflammasome activation. J Immunol (2013) 191(10):5230-8. doi:10.4049/jimmunol.1301490
140. Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature (2011) 469(7329):221-5. doi:10.1038/nature09663
141. Ferger AI, Campanelli L, Reimer V, Muth KN, Merdian I, Ludolph AC, et al. Effects of mitochondrial dysfunction on the immunological properties of microglia. J Neuroinflammation (2010) 7:45. doi:10.1186/1742-2094-7-45
142. Ryu JK, Nagai A, Kim J, Lee MC, McLarnon JG, Kim SU. Microglial activation and cell death induced by the mitochondrial toxin 3-nitropropionic acid: in vitro and in vivo studies. Neurobiol Dis (2003) 12(2):121-32. doi:10.1016/S0969-9961(03)00002-0
143. Yi PL, Tsai CH, Lu MK, Liu HJ, Chen YC, Chang FC. Interleukin-1beta mediates sleep alteration in rats with rotenone-induced parkinsonism. Sleep (2007) 30(4):413-25. doi:10.1093/sleep/30.4.413
144. Kastl L, Sauer S, Beissbarth T, Becker M, Krammer P, Gulow K. TNF-a stimulation enhances ROS-dependent cell migration via NF-κB activation in liver cells. Free Radic Biol Med (2014) 75(Suppl 1):S32. doi:10.1016/j.freeradbiomed.2014.10.765
145. Kastl L, Sauer SW, Ruppert T, Beissbarth T, Becker MS, Suss D, et al. TNF-alpha mediates mitochondrial uncoupling and enhances ROS-dependent cell migration via NF-kappaB activation in liver cells. FEBS Lett (2014) 588(1):175-83. doi:10.1016/j.febslet.2013.11.033
146. Goossens V, Stange G, Moens K, Pipeleers D, Grooten J. Regulation of tumor necrosis factor-induced, mitochondria-and reactive oxygen species-dependent cell death by the electron flux through the electron transport chain complex I. Antioxid Redox Signal (1999) 1(3):285-95. doi:10.1089/ars.1999.1.3-285
147. Chen XH, Zhao YP, Xue M, Ji CB, Gao CL, Zhu JG, et al. TNF-alpha induces mitochondrial dysfunction in 3T3-L1 adipocytes. Mol Cell Endocrinol (2010) 328(1-2):63-9. doi:10.1016/j.mce.2010.07.005
148. Higuchi M, Proske RJ, Yeh ET. Inhibition of mitochondrial respiratory chain complex I by TNF results in cytochrome c release, membrane permeability transition, and apoptosis. Oncogene (1998) 17(19):2515-24. doi:10.1038/sj.onc.1202485
149. Doll DN, Rellick SL, Barr TL, Ren X, Simpkins JW. Rapid mitochondrial dysfunction mediates TNF-alpha-induced neurotoxicity. J Neurochem (2015) 132(4):443-51. doi:10.1111/jnc.13008
150. Yasuhara R, Miyamoto Y, Akaike T, Akuta T, Nakamura M, Takami M, et al. Interleukin-1beta induces death in chondrocyte-like ATDC5 cells through mitochondrial dysfunction and energy depletion in a reactive nitrogen and oxygen species-dependent manner. Biochem J (2005) 389(Pt 2):315-23. doi:10.1042/BJ20041996
151. Yang D, Elner SG, Bian ZM, Till GO, Petty HR, Elner VM. Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells. Exp Eye Res (2007) 85(4):462-72. doi:10.1016/j.exer.2007.06.013
152. Noh H, Jeon J, Seo H. Systemic injection of LPS induces region-specific neuroinflammation and mitochondrial dysfunction in normal mouse brain. Neurochem Int (2014) 69:35-40. doi:10.1016/j.neuint.2014.02.008
153. Hokari Y, Seki T, Nakano H, Matsuo Y, Fukamizu A, Munekata E, et al. Isolation and identification of novel neutrophil-activating cryptides hidden in mitochondrial cytochrome c. Protein Pept Lett (2012) 19(6):680-7. doi:10.2174/092986612800494048
154. Marutani T, Hattori T, Tsutsumi K, Koike Y, Harada A, Noguchi K, et al. Mitochondrial protein-derived cryptides: are endogenous N-formylated peptides including mitocryptide-2 components of mitochondrial damage-associated molecular patterns? Biopolymers (2016) 106(4):580-7. doi:10.1002/bip.22788
155. Seki T, Fukamizu A, Kiso Y, Mukai H. Mitocryptide-2, a neutrophil-activating cryptide, is a specific endogenous agonist for formyl-peptide receptor-like 1. Biochem Biophys Res Commun (2011) 404(1):482-7. doi:10.1016/j.bbrc.2010.12.007
156. Pinti M, Cevenini E, Nasi M, De Biasi S, Salvioli S, Monti D, et al. Circulating mitochondrial DNA increases with age and is a familiar trait: Implications for "inflamm-aging". Eur J Immunol (2014) 44(5):1552-62. doi:10.1002/eji.201343921
157. Podlesniy P, Figueiro-Silva J, Llado A, Antonell A, Sanchez-Valle R, Alcolea D, et al. Low cerebrospinal fluid concentration of mitochondrial DNA in preclinical Alzheimer disease. Ann Neurol (2013) 74(5):655-68. doi:10.1002/ana.23955
158. Pyle A, Brennan R, Kurzawa-Akanbi M, Yarnall A, Thouin A, Mollenhauer B, et al. Reduced cerebrospinal fluid mitochondrial DNA is a biomarker for early-stage Parkinson's disease. Ann Neurol (2015) 78(6):1000-4. doi:10.1002/ana.24515
159. Aichbichler BW, Petritsch W, Reicht GA, Wenzl HH, Eherer AJ, Hinterleitner TA, et al. Anti-cardiolipin antibodies in patients with inflammatory bowel disease. Dig Dis Sci (1999) 44(4):852-6. doi:10.1023/A:1026646816672
160. Erkkila AT, Narvanen O, Lehto S, Uusitupa MI, Yla-Herttuala S. Autoantibodies against oxidized low-density lipoprotein and cardiolipin in patients with coronary heart disease. Arterioscler Thromb Vasc Biol (2000) 20(1):204-9. doi:10.1161/01.ATV.20.1.204
161. Koutroubakis IE, Petinaki E, Anagnostopoulou E, Kritikos H, Mouzas IA, Kouroumalis EA, et al. Anti-cardiolipin and anti-beta2-glycoprotein I antibodies in patients with inflammatory bowel disease. Dig Dis Sci (1998) 43(11):2507-12. doi:10.1023/A:1026602803622
162. Nityanand S, Bergmark C, de Faire U, Swedenborg J, Holm G, Lefvert AK. Antibodies against endothelial cells and cardiolipin in young patients with peripheral atherosclerotic disease. J Intern Med (1995) 238(5):437-43. doi:10.1111/j.1365-2796.1995.tb01221.x
163. Thong BY, Chng HH, Ang CL, Ho MS. Recurrent venous thromboses, anti-cardiolipin antibodies and Crohn's disease. QJM (2002) 95(4):253-5. doi:10.1093/qjmed/95.4.253-a
164. Wan M, Hua X, Su J, Thiagarajan D, Frostegard AG, Haeggstrom JZ, et al. Oxidized but not native cardiolipin has pro-inflammatory effects, which are inhibited by Annexin A5. Atherosclerosis (2014) 235(2):592-8. doi:10.1016/j.atherosclerosis.2014.05.913
165. Wolf P, Gretler J, Aglas F, Auer-Grumbach P, Rainer F. Anticardiolipin antibodies in rheumatoid arthritis: their relation to rheumatoid nodules and cutaneous vascular manifestations. Br J Dermatol (1994) 131(1):48-51. doi:10.1111/j.1365-2133.1994.tb08456.x
166. Wu R, Nityanand S, Berglund L, Lithell H, Holm G, Lefvert AK. Antibodies against cardiolipin and oxidatively modified LDL in 50-year-old men predict myocardial infarction. Arterioscler Thromb Vasc Biol (1997) 17(11):3159-63. doi:10.1161/01.ATV.17.11.3159
167. Riteau N, Gasse P, Fauconnier L, Gombault A, Couegnat M, Fick L, et al. Extracellular ATP is a danger signal activating P2X7 receptor in lung inflammation and fibrosis. Am J Respir Crit Care Med (2010) 182(6):774-83. doi:10.1164/rccm.201003-0359OC
168. Stachon P, Geis S, Peikert A, Heidenreich A, Michel NA, Unal F, et al. Extracellular ATP induces vascular inflammation and atherosclerosis via purinergic receptor Y2 in mice. Arterioscler Thromb Vasc Biol (2016) 36(8):1577-86. doi:10.1161/ATVBAHA.115.307397
169. Raoof M, Zhang Q, Itagaki K, Hauser CJ. Mitochondrial peptides are potent immune activators that activate human neutrophils via FPR-1. J Trauma (2010) 68(6):1328-32, discussion 32-4. doi:10.1097/TA.0b013e3181dcd28d
170. Gao X, Hu X, Qian L, Yang S, Zhang W, Zhang D, et al. Formyl-methionyl-leucyl-phenylalanine-induced dopaminergic neurotoxicity via microglial activation: a mediator between peripheral infection and neurodegeneration? Environ Health Perspect (2008) 116(5):593-8. doi:10.1289/ehp.11031
171. Pan ZK, Chen LY, Cochrane CG, Zuraw BL. fMet-Leu-Phe stimulates proinflammatory cytokine gene expression in human peripheral blood monocytes: the role of phosphatidylinositol 3-kinase. J Immunol (2000) 164(1):404-11. doi:10.4049/jimmunol.164.1.404
172. Sodhi A, Biswas SK. fMLP-induced in vitro nitric oxide production and its regulation in murine peritoneal macrophages. J Leukoc Biol (2002) 71(2):262-70
173. Little JP, Simtchouk S, Schindler SM, Villanueva EB, Gill NE, Walker DG, et al. Mitochondrial transcription factor A (Tfam) is a pro-inflammatory extracellular signaling molecule recognized by brain microglia. Mol Cell Neurosci (2014) 60:88-96. doi:10.1016/j.mcn.2014.04.003
174. Chaung WW, Wu R, Ji Y, Dong W, Wang P. Mitochondrial transcription factor A is a proinflammatory mediator in hemorrhagic shock. Int J Mol Med (2012) 30(1):199-203. doi:10.3892/ijmm.2012.959
175. Pullerits R, Bokarewa M, Jonsson IM, Verdrengh M, Tarkowski A. Extracellular cytochrome c, a mitochondrial apoptosis-related protein, induces arthritis. Rheumatology (2005) 44(1):32-9. doi:10.1093/rheumatology/keh406
176. Krysko DV, Agostinis P, Krysko O, Garg AD, Bachert C, Lambrecht BN, et al. Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation. Trends Immunol (2011) 32(4):157-64. doi:10.1016/j.it.2011.01.005
177. Wilkins HM, Carl SM, Weber SG, Ramanujan SA, Festoff BW, Linseman DA, et al. Mitochondrial lysates induce inflammation and Alzheimer's disease-relevant changes in microglial and neuronal cells. J Alzheimers Dis (2015) 45(1):305-18. doi:10.3233/JAD-142334
178. Wilkins HM, Koppel SJ, Weidling IW, Roy N, Ryan LN, Stanford JA, et al. Extracellular mitochondria and mitochondrial components act as damage-associated molecular pattern molecules in the mouse brain. J Neuroimmune Pharmacol (2016) 11(4):622-8. doi:10.1007/s11481-016-9704-7
179. Kumar DK, Choi SH, Washicosky KJ, Eimer WA, Tucker S, Ghofrani J, et al. Amyloid-beta peptide protects against microbial infection in mouse and worm models of Alzheimer's disease. Sci Transl Med (2016) 8(340):340ra72. doi:10.1126/scitranslmed.aaf1059
180. Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, et al. The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One (2010) 5(3):e9505. doi:10.1371/journal.pone.0009505
181. Tapiola T, Alafuzoff I, Herukka SK, Parkkinen L, Hartikainen P, Soininen H, et al. Cerebrospinal fluid (beta)-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch Neurol (2009) 66(3):382-9. doi:10.1001/archneurol.2008.596
182. Galasko D, Chang L, Motter R, Clark CM, Kaye J, Knopman D, et al. High cerebrospinal fluid tau and low amyloid beta42 levels in the clinical diagnosis of Alzheimer disease and relation to apolipoprotein E genotype. Arch Neurol (1998) 55(7):937-45. doi:10.1001/archneur.55.7.937
183. Davis CH, Kim KY, Bushong EA, Mills EA, Boassa D, Shih T, et al. Transcellular degradation of axonal mitochondria. Proc Natl Acad Sci U S A (2014) 111(26):9633-8. doi:10.1073/pnas.1404651111
184. Hayakawa K, Esposito E, Wang X, Terasaki Y, Liu Y, Xing C, et al. Transfer of mitochondria from astrocytes to neurons after stroke. Nature (2016) 535(7613):551-5. doi:10.1038/nature18928