Adaptive responses of neuronal mitochondria to bioenergetic challenges: Roles in neuroplasticity and disease resistance

Free Radical Biology and Medicine

Volumn 102, Issue , 2017, Pages 203-216

  Raefsky, Sophia M ^a   Mattson, Mark P ^a,b  

^a NATIONAL INSTITUTE ON AGING   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

3 hydroxybutyrate; Aerobic exercise; Autophagy; CREB; Hormesis; Intermittent fasting; Mitochondrial biogenesis; PGC 1

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; FATTY ACID; GLUTAMIC ACID;

ALZHEIMER DISEASE; BIOENERGY; BRAIN FUNCTION; BRAIN INJURY; BRAIN MITOCHONDRION; CALORIC INTAKE; CELLULAR STRESS RESPONSE; CEREBROVASCULAR ACCIDENT; DEGENERATIVE DISEASE; DIET RESTRICTION; DISEASE RESISTANCE; EXERCISE; HUMAN; HUNTINGTON CHOREA; KETOGENESIS; NERVE CELL; NERVE CELL PLASTICITY; NERVE DEGENERATION; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; SEDENTARY LIFESTYLE; STRESS; TRAUMATIC BRAIN INJURY; DNA REPAIR; ENERGY METABOLISM; GENETICS; METABOLISM; MITOCHONDRION; ORGANELLE BIOGENESIS; PATHOLOGY; SIGNAL TRANSDUCTION;

DISEASE RESISTANCE; DNA REPAIR; ENERGY METABOLISM; HUMANS; MITOCHONDRIA; NEURODEGENERATIVE DISEASES; NEURONAL PLASTICITY; NEURONS; ORGANELLE BIOGENESIS; SIGNAL TRANSDUCTION;

EID: 85002388844     PISSN: 08915849     EISSN: 18734596     Source Type: Journal    
DOI: 10.1016/j.freeradbiomed.2016.11.045     Document Type: Review

References (205)

1. [1] Longo, V.D., Mattson, M.P., Fasting: molecular mechanisms and clinical applications. Cell Metab. 19:2 (2014), 181–192.
2. [2] Mattson, M.P., Lifelong brain health is a lifelong challenge: from evolutionary principles to empirical evidence. Ageing Res. Rev. 20 (2015), 37–45.
3. [3] Metz, M.C., et al. Seasonal patterns of predation for gray wolves in the multi-prey system of Yellowstone National Park. J. Anim. Ecol. 81:3 (2012), 553–563.
4. [4] Tveraa, T., et al. An examination of a compensatory relationship between food limitation and predation in semi-domestic reindeer. Oecologia 137:3 (2003), 370–376.
5. [5] Mattson, M.P., Superior pattern processing is the essence of the evolved human brain. Front. Neurosci., 8, 2014, 265.
6. [6] Genovesio, A., Wise, S.P., Passingham, R.E., Prefrontal-parietal function: from foraging to foresight. Trends Cogn. Sci. 18:2 (2014), 72–81.
7. [7] Morgan, T.J., et al. Experimental evidence for the co-evolution of hominin tool-making teaching and language. Nat. Commun., 6, 2015, 6029.
8. [8] Irrcher, I., et al. Regulation of mitochondrial biogenesis in muscle by endurance exercise. Sports Med. 33:11 (2003), 783–793.
9. [9] Radak, Z., et al. Oxygen consumption and usage during physical exercise: the balance between oxidative stress and ROS-dependent adaptive signaling. Antioxid. Redox Signal. 18:10 (2013), 1208–1246.
10. [10] Wan, R., Camandola, S., Mattson, M.P., Intermittent food deprivation improves cardiovascular and neuroendocrine responses to stress in rats. J. Nutr. 133:6 (2003), 1921–1929.
11. [11] Volek, J.S., Noakes, T., Phinney, S.D., Rethinking fat as a fuel for endurance exercise. Eur. J. Sport Sci. 15:1 (2015), 13–20.
12. [12] Mattson, M.P., Energy intake and exercise as determinants of brain health and vulnerability to injury and disease. Cell Metab. 16:6 (2012), 706–722.
13. [13] Mattson, M.P., Gleichmann, M., Cheng, A., Mitochondria in neuroplasticity and neurological disorders. Neuron 60:5 (2008), 748–766.
14. [14] Bernardo, T.C., et al. Physical exercise and brain mitochondrial fitness: the possible role against Alzheimer's disease. Brain Pathol. 26:5 (2016), 648–663.
15. [15] Fontan-Lozano, A., et al. Molecular bases of caloric restriction regulation of neuronal synaptic plasticity. Mol. Neurobiol. 38:2 (2008), 167–177.
16. [16] Rolfe, D.F., Brown, G.C., Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol. Rev. 77:3 (1997), 731–758.
17. [17] Chan, D.C., Mitochondria: dynamic organelles in disease, aging, and development. Cell 125:7 (2006), 1241–1252.
18. [18] Hoppins, S., Lackner, L., Nunnari, J., The machines that divide and fuse mitochondria. Annu. Rev. Biochem. 76 (2007), 751–780.
19. [19] Knott, A.B., et al. Mitochondrial fragmentation in neurodegeneration. Nat. Rev. Neurosci. 9:7 (2008), 505–518.
20. [20] Stranahan, A.M., et al. Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats. Hippocampus 18:11 (2008), 1085–1088.
21. [21] Marques-Aleixo, I., et al. Physical exercise as a possible strategy for brain protection: evidence from mitochondrial-mediated mechanisms. Prog. Neurobiol. 99:2 (2012), 149–162.
22. [22] Cheng, A., et al. Mitochondrial SIRT3 mediates adaptive responses of neurons to exercise and metabolic and excitatory challenges. Cell Metab. 23:1 (2016), 128–142.
23. [23] Monteiro, J.P., Oliveira, P.J., Jurado, A.S., Mitochondrial membrane lipid remodeling in pathophysiology: a new target for diet and therapeutic interventions. Prog. Lipid Res. 52:4 (2013), 513–528.
24. [24] Mattson, M.P., Roles of the lipid peroxidation product 4-hydroxynonenal in obesity, the metabolic syndrome, and associated vascular and neurodegenerative disorders. Exp. Gerontol. 44:10 (2009), 625–633.
25. [25] Poli, G., et al. 4-hydroxynonenal: a membrane lipid oxidation product of medicinal interest. Med. Res. Rev. 28:4 (2008), 569–631.
26. [26] Petersen, D.R., Doorn, J.A., Reactions of 4-hydroxynonenal with proteins and cellular targets. Free Radic. Biol. Med. 37:7 (2004), 937–945.
27. [27] Chen, H., Chan, D.C., Mitochondrial dynamics – fusion, fission, movement, and mitophagy – in neurodegenerative diseases. Hum. Mol. Genet. 18:R2 (2009), R169–R176.
28. [28] Westermann, B., Mitochondrial dynamics in model organisms: what yeasts, worms and flies have taught us about fusion and fission of mitochondria. Semin. Cell Dev. Biol. 21:6 (2010), 542–549.
29. [29] Detmer, S.A., Chan, D.C., Functions and dysfunctions of mitochondrial dynamics. Nat. Rev. Mol. Cell Biol. 8:11 (2007), 870–879.
30. [30] Youle, R.J., Narendra, D.P., Mechanisms of mitophagy. Nat. Rev. Mol. Cell Biol. 12:1 (2011), 9–14.
31. [31] Burte, F., et al. Disturbed mitochondrial dynamics and neurodegenerative disorders. Nat. Rev. Neurol. 11:1 (2015), 11–24.
32. [32] Onyango, I.G., Dennis, J., Khan, S.M., Mitochondrial dysfunction in Alzheimer's disease and the rationale for bioenergetics based therapies. Aging Dis. 7:2 (2016), 201–214.
33. [33] Scarpulla, R.C., Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol. Rev. 88:2 (2008), 611–638.
34. [34] Ashrafi, G., Schwarz, T.L., The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ. 20:1 (2013), 31–42.
35. [35] Cheng, A., et al. Involvement of PGC-1alpha in the formation and maintenance of neuronal dendritic spines. Nat. Commun., 3, 2012, 1250.
36. [36] Hood, D.A., et al. Unravelling the mechanisms regulating muscle mitochondrial biogenesis. Biochem. J. 473:15 (2016), 2295–2314.
37. [37] Jacobson, S.La.M., Developmental Neurobiology. 2005, Springer, New York.
38. [38] Yamaguchi, Y., Miura, M., Programmed cell death and caspase functions during neural development. Curr. Top. Dev. Biol. 114 (2015), 159–184.
39. [39] Yuste, R., Bonhoeffer, T., Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu. Rev. Neurosci. 24 (2001), 1071–1089.
40. [40] Stranahan, A.M., et al. Voluntary exercise and caloric restriction enhance hippocampal dendritic spine density and BDNF levels in diabetic mice. Hippocampus 19:10 (2009), 951–961.
41. [41] Mattson, M.P., Partin, J., Evidence for mitochondrial control of neuronal polarity. J. Neurosci. Res. 56:1 (1999), 8–20.
42. [42] Li, Z., et al. The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119:6 (2004), 873–887.
43. [43] Kambe, Y., Miyata, A., Role of mitochondrial activation in PACAP dependent neurite outgrowth. J. Mol. Neurosci. 48:3 (2012), 550–557.
44. [44] Marosi, K., Mattson, M.P., BDNF mediates adaptive brain and body responses to energetic challenges. Trends Endocrinol. Metab. 25:2 (2014), 89–98.
45. [45] Su, B., et al. Brain-derived neurotrophic factor (BDNF)-induced mitochondrial motility arrest and presynaptic docking contribute to BDNF-enhanced synaptic transmission. J. Biol. Chem. 289:3 (2014), 1213–1226.
46. [46] Stephen, T.L., et al. Miro1 regulates activity-driven positioning of mitochondria within astrocytic processes apposed to synapses to regulate intracellular calcium signaling. J. Neurosci. 35:48 (2015), 15996–16011.
47. [47] Sun, T., et al. Motile axonal mitochondria contribute to the variability of presynaptic strength. Cell Rep. 4:3 (2013), 413–419.
48. [48] Chan, S.L., et al. Mitochondrial uncoupling protein-4 regulates calcium homeostasis and sensitivity to store depletion-induced apoptosis in neural cells. J. Biol. Chem. 281:49 (2006), 37391–37403.
49. [49] Liu, D., et al. Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress. Neuromol. Med. 8:3 (2006), 389–414.
50. [50] Hermes, G., et al. Role of mitochondrial uncoupling protein-2 (UCP2) in higher brain functions, neuronal plasticity and network oscillation. Mol. Metab. 5:6 (2016), 415–421.
51. [51] Dietrich, M.O., Andrews, Z.B., Horvath, T.L., Exercise-induced synaptogenesis in the hippocampus is dependent on UCP2-regulated mitochondrial adaptation. J. Neurosci. 28:42 (2008), 10766–10771.
52. [52] Massaad, C.A., et al. Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease. Proc. Natl. Acad. Sci. USA 106:32 (2009), 13576–13581.
53. [53] Stranahan, A.M., Mattson, M.P., Recruiting adaptive cellular stress responses for successful brain ageing. Nat. Rev. Neurosci. 13:3 (2012), 209–216.
54. [54] Fusco, S., et al. A role for neuronal cAMP responsive-element binding (CREB)-1 in brain responses to calorie restriction. Proc. Natl. Acad. Sci. USA 109:2 (2012), 621–626.
55. [55] Eckert, M.J., Abraham, W.C., Effects of environmental enrichment exposure on synaptic transmission and plasticity in the hippocampus. Curr. Top. Behav. Neurosci. 15 (2013), 165–187.
56. [56] Malvache, A., et al. Awake hippocampal reactivations project onto orthogonal neuronal assemblies. Science 353:6305 (2016), 1280–1283.
57. [57] Radak, Z., et al. Exercise plays a preventive role against Alzheimer's disease. J. Alzheimers Dis. 20:3 (2010), 777–783.
58. [58] van Praag, H., Kempermann, G., Gage, F.H., Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci. 2:3 (1999), 266–270.
59. [59] Cotman, C.W., Berchtold, N.C., Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 25:6 (2002), 295–301.
60. [60] van Praag, H., et al. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc. Natl. Acad. Sci. USA 96:23 (1999), 13427–13431.
61. [61] Lopez-Lopez, C., LeRoith, D., Torres-Aleman, I., Insulin-like growth factor I is required for vessel remodeling in the adult brain. Proc. Natl. Acad. Sci. USA 101:26 (2004), 9833–9838.
62. [62] Eggermont, L., et al. Exercise, cognition and Alzheimer's disease: more is not necessarily better. Neurosci. Biobehav. Rev. 30:4 (2006), 562–575.
63. [63] Ratey, J.J., Loehr, J.E., The positive impact of physical activity on cognition during adulthood: a review of underlying mechanisms, evidence and recommendations. Rev. Neurosci. 22:2 (2011), 171–185.
64. [64] Steiner, J.L., et al. Exercise training increases mitochondrial biogenesis in the brain. J. Appl. Physiol. 111:4 (1985), 1066–1071.
65. [65] Marosi, K., et al. Long-term exercise treatment reduces oxidative stress in the hippocampus of aging rats. Neuroscience 226 (2012), 21–28.
66. [66] E, L., Burns, J.M., Swerdlow, R.H., Effect of high-intensity exercise on aged mouse brain mitochondria, neurogenesis, and inflammation. Neurobiol. Aging 35:11 (2014), 2574–2583.
67. [67] Marques-Aleixo, I., et al. Physical exercise improves brain cortex and cerebellum mitochondrial bioenergetics and alters apoptotic, dynamic and auto(mito)phagy markers. Neuroscience 301 (2015), 480–495.
68. [68] Ding, Q., et al. Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function. Neuroscience 140:3 (2006), 823–833.
69. [69] Kirchner, L., et al. Hippocampal metabolic proteins are modulated in voluntary and treadmill exercise rats. Exp. Neurol. 212:1 (2008), 145–151.
70. [70] Mattson, M.P., et al. Meal frequency and timing in health and disease. Proc. Natl. Acad. Sci. USA 111:47 (2014), 16647–16653.
71. [71] Sohal, R.S., et al. Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse. Mech. Ageing Dev. 74:1–2 (1994), 121–133.
72. [72] Peterson, C.M., Johannsen, D.L., Ravussin, E., Skeletal muscle mitochondria and aging: a review. J. Aging Res., 2012, 2012, 194821.
73. [73] Gonzalez-Freire, M., et al. The neuromuscular junction: aging at the crossroad between nerves and muscle. Front. Aging Neurosci., 6, 2014, 208.
74. [74] Yu, Z., et al. The endoplasmic reticulum stress-responsive protein GRP78 protects neurons against excitotoxicity and apoptosis: suppression of oxidative stress and stabilization of calcium homeostasis. Exp. Neurol. 155:2 (1999), 302–314.
75. [75] Qin, W., et al. Calorie restriction attenuates Alzheimer's disease type brain amyloidosis in Squirrel monkeys (Saimiri sciureus). J. Alzheimers Dis. 10:4 (2006), 417–422.
76. [76] Qin, W., et al. Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J. Biol. Chem. 281:31 (2006), 21745–21754.
77. [77] Duan, W., Mattson, M.P., Dietary restriction and 2-deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson's disease. J. Neurosci. Res. 57:2 (1999), 195–206.
78. [78] Halagappa, V.K., et al. Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease. Neurobiol. Dis. 26:1 (2007), 212–220.
79. [79] Arumugam, T.V., et al. Age and energy intake interact to modify cell stress pathways and stroke outcome. Ann. Neurol. 67:1 (2010), 41–52.
80. [80] Griffioen, K.J., et al. Dietary energy intake modifies brainstem autonomic dysfunction caused by mutant alpha-synuclein. Neurobiol. Aging 34:3 (2013), 928–935.
81. [81] Guo, Z.H., Mattson, M.P., Neurotrophic factors protect cortical synaptic terminals against amyloid and oxidative stress-induced impairment of glucose transport, glutamate transport and mitochondrial function. Cereb. Cortex 10:1 (2000), 50–57.
82. [82] Sun, J., Ren, X., Simpkins, J.W., Sequential upregulation of superoxide dismutase 2 and heme oxygenase 1 by tert-butylhydroquinone protects mitochondria during oxidative stress. Mol. Pharmacol. 88:3 (2015), 437–449.
83. [83] Qiu, X., et al. Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab. 12:6 (2010), 662–667.
84. [84] Amigo, I., et al. Caloric restriction increases brain mitochondrial calcium retention capacity and protects against excitotoxicity. Aging Cell, 2016, 10.1111/acel.12527 (Epub ahead of print).
85. [85] Cunnane, S., et al. Brain fuel metabolism, aging, and Alzheimer's disease. Nutrition 27:1 (2011), 3–20.
86. [86] Seyfried, T.N., Mukherjee, P., Targeting energy metabolism in brain cancer: review and hypothesis. Nutr. Metab., 2, 2005, 30.
87. [87] Sullivan, P.G., et al. The ketogenic diet increases mitochondrial uncoupling protein levels and activity. Ann. Neurol. 55:4 (2004), 576–580.
88. [88] Maalouf, M., et al. Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation. Neuroscience 145:1 (2007), 256–264.
89. [89] Maalouf, M., Rho, J.M., Mattson, M.P., The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res. Rev. 59:2 (2009), 293–315.
90. [90] Yudkoff, M., et al. The ketogenic diet and brain metabolism of amino acids: relationship to the anticonvulsant effect. Annu. Rev. Nutr. 27 (2007), 415–430.
91. [91] Marosi, K., et al. 3-Hydroxybutyrate regulates energy metabolism and induces BDNF expression in cerebral cortical neurons. J. Neurochem., 2016, 14.
92. [92] Newman, J.C., Verdin, E., Ketone bodies as signaling metabolites. Trends Endocrinol. Metab. 25:1 (2014), 42–52.
93. [93] McCarty, M.F., DiNicolantonio, J.J., O'Keefe, J.H., Ketosis may promote brain macroautophagy by activating Sirt1 and hypoxia-inducible factor-1. Med. Hypotheses 85:5 (2015), 631–639.
94. [94] Hankey, G.J., Nutrition and the risk of stroke. Lancet Neurol. 11:1 (2012), 66–81.
95. [95] Mayeux, R., Stern, Y., Epidemiology of Alzheimer disease. Cold Spring Harb. Perspect. Med., 2(8), 2012.
96. [96] Mattson, M.P., Interventions that improve body and brain bioenergetics for Parkinson's disease risk reduction and therapy. J. Park. Dis. 4:1 (2014), 1–13.
97. [97] Block, G., Rosenberger, W.F., Patterson, B.H., Calories, fat and cholesterol: intake patterns in the US population by race, sex and age. Am. J. Public Health 78:9 (1988), 1150–1155.
98. [98] Grant, W.B., Using multicountry ecological and observational studies to determine dietary risk factors for Alzheimer's disease. J. Am. Coll. Nutr. 35:5 (2016), 476–489.
99. [99] Molteni, R., et al. A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience 112:4 (2002), 803–814.
100. [100] van den Berg, E., et al. Cognitive functioning in elderly persons with type 2 diabetes and metabolic syndrome: the Hoorn study. Dement. Geriatr. Cogn. Disord. 26:3 (2008), 261–269.
101. [101] Gazdzinski, S., et al. Body mass index and magnetic resonance markers of brain integrity in adults. Ann. Neurol. 63:5 (2008), 652–657.
102. [102] Chung, J.Y., et al. The effect of exercise on trkA in the contralateral hemisphere of the ischemic rat brain. Brain Res. 1353 (2010), 187–193.
103. [103] Robertson, C.L., et al. Mitochondrial mechanisms of cell death and neuroprotection in pediatric ischemic and traumatic brain injury. Exp. Neurol. 218:2 (2009), 371–380.
104. [104] Broughton, B.R., Reutens, D.C., Sobey, C.G., Apoptotic mechanisms after cerebral ischemia. Stroke 40:5 (2009), e331–e339.
105. [105] Onyango, I.G., et al. Regulation of neuron mitochondrial biogenesis and relevance to brain health. Biochim. Biophys. Acta 1802:1 (2010), 228–234.
106. [106] Hillered, L., Ernster, L., Respiratory activity of isolated rat brain mitochondria following in vitro exposure to oxygen radicals. J. Cereb. Blood Flow Metab. 3:2 (1983), 207–214.
107. [107] Rosenthal, R.E., et al. Cerebral ischemia and reperfusion: prevention of brain mitochondrial injury by lidoflazine. J. Cereb. Blood Flow Metab. 7:6 (1987), 752–758.
108. [108] Sims, N.R., Selective impairment of respiration in mitochondria isolated from brain subregions following transient forebrain ischemia in the rat. J. Neurochem. 56:6 (1991), 1836–1844.
109. [109] Thurman, D.J., et al. Traumatic brain injury in the United States: a public health perspective. J. Head Trauma Rehabil. 14:6 (1999), 602–615.
110. [110] Langlois, J.A., Rutland-Brown, W., Thomas, K.E., The incidence of traumatic brain injury among children in the United States: differences by race. J. Head Trauma Rehabil. 20:3 (2005), 229–238.
111. [111] Davis, L.M., et al. Fasting is neuroprotective following traumatic brain injury. J. Neurosci. Res. 86:8 (2008), 1812–1822.
112. [112] Robertson, C.L., et al. The potential role of mitochondria in pediatric traumatic brain injury. Dev. Neurosci. 28:4–5 (2006), 432–446.
113. [113] Robertson, C.L., Saraswati, M., Fiskum, G., Mitochondrial dysfunction early after traumatic brain injury in immature rats. J. Neurochem. 101:5 (2007), 1248–1257.
114. [114] Laird, M.D., et al. Augmentation of normal and glutamate-impaired neuronal respiratory capacity by exogenous alternative biofuels. Transl. Stroke Res. 4:6 (2013), 643–651.
115. [115] Khrapko, K., Turnbull, D., Mitochondrial DNA mutations in aging. Prog. Mol. Biol. Transl. Sci. 127 (2014), 29–62.
116. [116] Fang, E.F., et al. Nuclear DNA damage signalling to mitochondria in ageing. Nat. Rev. Mol. Cell Biol. 17:5 (2016), 308–321.
117. [117] Tanzi, R.E., Bertram, L., Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell 120:4 (2005), 545–555.
118. [118] Castellani, R.J., Rolston, R.K., Smith, M.A., Alzheimer disease. Dis. Mon. 56:9 (2010), 484–546.
119. [119] Selkoe, D.J., Alzheimer's disease results from the cerebral accumulation and cytotoxicity of amyloid beta-protein. J. Alzheimers Dis. 3:1 (2001), 75–80.
120. [120] Mattson, M.P., Pathways towards and away from Alzheimer's disease. Nature 430:7000 (2004), 631–639.
121. [121] Walsh, D.M., Selkoe, D.J., A beta oligomers – a decade of discovery. J. Neurochem. 101:5 (2007), 1172–1184.
122. [122] Bezprozvanny, I., Mattson, M.P., Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease. Trends Neurosci. 31:9 (2008), 454–463.
123. [123] Goedert, M., Ghetti, B., Spillantini, M.G., Frontotemporal dementia: implications for understanding Alzheimer disease. Cold Spring Harb. Perspect. Med., 2(2), 2012, a006254.
124. [124] Hauptmann, S., et al. Mitochondrial dysfunction: an early event in Alzheimer pathology accumulates with age in AD transgenic mice. Neurobiol. Aging 30:10 (2009), 1574–1586.
125. [125] Parker, W.D. Jr., Parks, J.K., Cytochrome c oxidase in Alzheimer's disease brain: purification and characterization. Neurology 45:3 Pt 1 (1995), 482–486.
126. [126] Gibson, G.E., Sheu, K.F., Blass, J.P., Abnormalities of mitochondrial enzymes in Alzheimer disease. J. Neural Transm. 105:8–9 (1998), 855–870.
127. [127] Maurer, I., Zierz, S., Moller, H.J., A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients. Neurobiol. Aging 21:3 (2000), 455–462.
128. [128] Nixon, R.A., The role of autophagy in neurodegenerative disease. Nat. Med. 19:8 (2013), 983–997.
129. [129] Kapogiannis, D., Mattson, M.P., Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease. Lancet Neurol. 10:2 (2011), 187–198.
130. [130] Mark, R.J., et al. Amyloid beta-peptide impairs glucose transport in hippocampal and cortical neurons: involvement of membrane lipid peroxidation. J. Neurosci. 17:3 (1997), 1046–1054.
131. [131] Wilkins, H.M., Swerdlow, R.H., Amyloid precursor protein processing and bioenergetics. Brain Res. Bull., 2016.
132. [132] Schmitt, K., et al. Insights into mitochondrial dysfunction: aging, amyloid-beta, and tau-A deleterious trio. Antioxid. Redox Signal. 16:12 (2012), 1456–1466.
133. [133] Mattson, M.P., et al. 4-Hydroxynonenal, a product of lipid peroxidation, inhibits dephosphorylation of the microtubule-associated protein tau. Neuroreport 8:9–10 (1997), 2275–2281.
134. [134] Gwon, A.R., et al. Oxidative lipid modification of nicastrin enhances amyloidogenic gamma-secretase activity in Alzheimer's disease. Aging Cell 11:4 (2012), 559–568.
135. [135] Allen, S.J., Watson, J.J., Dawbarn, D., The neurotrophins and their role in Alzheimer's disease. Curr. Neuropharmacol. 9:4 (2011), 559–573.
136. [136] Sykora, P., et al. DNA polymerase beta deficiency leads to neurodegeneration and exacerbates Alzheimer disease phenotypes. Nucleic Acids Res. 43:2 (2015), 943–959.
137. [137] Caccamo, A., et al. Genetic reduction of mammalian target of rapamycin ameliorates Alzheimer's disease-like cognitive and pathological deficits by restoring hippocampal gene expression signature. J. Neurosci. 34:23 (2014), 7988–7998.
138. [138] Klingelhoefer, L., Reichmann, H., Pathogenesis of Parkinson disease – the gut-brain axis and environmental factors. Nat. Rev. Neurol. 11:11 (2015), 625–636.
139. [139] Hu, Q., Wang, G., Mitochondrial dysfunction in Parkinson's disease. Transl. Neurodegener., 5, 2016, 14.
140. [140] Jankovic, J., Parkinson's disease: clinical features and diagnosis. J. Neurol. Neurosurg. Psychiatry 79:4 (2008), 368–376.
141. [141] Halliwell, B., Jenner, P., Impaired clearance of oxidised proteins in neurodegenerative diseases. Lancet, 351(9114), 1998, 1510.
142. [142] Everse, J., Coates, P.W., Role of peroxidases in Parkinson disease: a hypothesis. Free Radic. Biol. Med. 38:10 (2005), 1296–1310.
143. [143] Ryan, B.J., et al. Mitochondrial dysfunction and mitophagy in Parkinson's: from familial to sporadic disease. Trends Biochem. Sci. 40:4 (2015), 200–210.
144. [144] Martinez, T.N., Greenamyre, J.T., Toxin models of mitochondrial dysfunction in Parkinson's disease. Antioxid. Redox Signal. 16:9 (2012), 920–934.
145. [145] Goldman, S.M., Environmental toxins and Parkinson's disease. Annu. Rev. Pharmacol. Toxicol. 54 (2014), 141–164.
146. [146] Walker, F.O., Huntington's disease. Lancet 369:9557 (2007), 218–228.
147. [147] Oliveira, J.M., et al. Mitochondrial dysfunction in Huntington's disease: the bioenergetics of isolated and in situ mitochondria from transgenic mice. J. Neurochem. 101:1 (2007), 241–249.
148. [148] Marie, C., et al. Fasting prior to transient cerebral ischemia reduces delayed neuronal necrosis. Metab. Brain Dis. 5:2 (1990), 65–75.
149. [149] Zhang, Q., et al. Early exercise affects mitochondrial transcription factors expression after cerebral ischemia in rats. Int. J. Mol. Sci. 13:2 (2012), 1670–1679.
150. [150] Zhang, Q., et al. Exercise induces mitochondrial biogenesis after brain ischemia in rats. Neuroscience 205 (2012), 10–17.
151. [151] Kim, M.W., et al. Exercise increased BDNF and trkB in the contralateral hemisphere of the ischemic rat brain. Brain Res. 1052:1 (2005), 16–21.
152. [152] Korde, A.S., et al. The mitochondrial uncoupler 2,4-dinitrophenol attenuates tissue damage and improves mitochondrial homeostasis following transient focal cerebral ischemia. J. Neurochem. 94:6 (2005), 1676–1684.
153. [153] Liu, D., et al. The mitochondrial uncoupler DNP triggers brain cell mTOR signaling network reprogramming and CREB pathway up-regulation. J. Neurochem. 134:4 (2015), 677–692.
154. [154] Yu, Z.F., Mattson, M.P., Dietary restriction and 2-deoxyglucose administration reduce focal ischemic brain damage and improve behavioral outcome: evidence for a preconditioning mechanism. J. Neurosci. Res. 57:6 (1999), 830–839.
155. [155] Puchowicz, M.A., et al. Neuroprotection in diet-induced ketotic rat brain after focal ischemia. J. Cereb. Blood Flow Metab. 28:12 (2008), 1907–1916.
156. [156] Liu, D., et al. Nicotinamide prevents NAD+ depletion and protects neurons against excitotoxicity and cerebral ischemia: NAD+ consumption by SIRT1 may endanger energetically compromised neurons. Neuromol. Med. 11:1 (2009), 28–42.
157. [157] Prins, M.L., Fujima, L.S., Hovda, D.A., Age-dependent reduction of cortical contusion volume by ketones after traumatic brain injury. J. Neurosci. Res. 82:3 (2005), 413–420.
158. [158] Pandya, J.D., et al. Post-injury administration of mitochondrial uncouplers increases tissue sparing and improves behavioral outcome following traumatic brain injury in rodents. J. Neurotrauma 24:5 (2007), 798–811.
159. [159] Sullivan, P.G., et al. Dietary supplement creatine protects against traumatic brain injury. Ann. Neurol. 48:5 (2000), 723–729.
160. [160] Hoane, M.R., et al. Nicotinamide treatment induces behavioral recovery when administered up to 4 hours following cortical contusion injury in the rat. Neuroscience 154:3 (2008), 861–868.
161. [161] Driscoll, I., Troncoso, J., Asymptomatic Alzheimer's disease: a prodrome or a state of resilience?. Curr. Alzheimer Res. 8:4 (2011), 330–335.
162. [162] Adlard, P.A., et al. Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease. J. Neurosci. 25:17 (2005), 4217–4221.
163. [163] Yuede, C.M., et al. Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg2576 mouse model of Alzheimer's disease. Neurobiol. Dis. 35:3 (2009), 426–432.
164. [164] Garcia-Mesa, Y., et al. Physical exercise protects against Alzheimer's disease in 3xTg-AD mice. J. Alzheimers Dis. 24:3 (2011), 421–454.
165. [165] Bo, H., et al. Exercise-induced neuroprotection of hippocampus in APP/PS1 transgenic mice via upregulation of mitochondrial 8-oxoguanine DNA glycosylase. Oxid. Med. Cell. Longev., 2014, 2014, 834502.
166. [166] Um, H.S., et al. Exercise training acts as a therapeutic strategy for reduction of the pathogenic phenotypes for Alzheimer's disease in an NSE/APPsw-transgenic model. Int. J. Mol. Med. 22:4 (2008), 529–539.
167. [167] Um, H.S., et al. Treadmill exercise represses neuronal cell death in an aged transgenic mouse model of Alzheimer's disease. Neurosci. Res. 69:2 (2011), 161–173.
168. [168] Leem, Y.H., et al. Repression of tau hyperphosphorylation by chronic endurance exercise in aged transgenic mouse model of tauopathies. J. Neurosci. Res. 87:11 (2009), 2561–2570.
169. [169] Mattson, M.P., Challenging oneself intermittently to improve health. Dose Response 12:4 (2014), 600–618.
170. [170] Liang, K.Y., et al. Exercise and Alzheimer's disease biomarkers in cognitively normal older adults. Ann. Neurol. 68:3 (2010), 311–318.
171. [171] Kashiwaya, Y., et al. A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease. Neurobiol. Aging 34:6 (2013), 1530–1539.
172. [172] Yin, J.X., et al. Ketones block amyloid entry and improve cognition in an Alzheimer's model. Neurobiol. Aging 39 (2016), 25–37.
173. [173] Reger, M.A., et al. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiol. Aging 25:3 (2004), 311–314.
174. [174] Yao, J., et al. 2-Deoxy-D-glucose treatment induces ketogenesis, sustains mitochondrial function, and reduces pathology in female mouse model of Alzheimer's disease. PLoS One, 6(7), 2011, e21788.
175. [175] Geisler, J.G., et al. DNP, mitochondrial uncoupling, and neuroprotection: a little dab'll do ya. Alzheimers Dement., 2016.
176. [176] Liu, D., et al. The KATP channel activator diazoxide ameliorates amyloid-beta and tau pathologies and improves memory in the 3xTgAD mouse model of Alzheimer's disease. J. Alzheimers Dis. 22:2 (2010), 443–457.
177. [177] Xu, Q., et al. Physical activities and future risk of Parkinson disease. Neurology 75:4 (2010), 341–348.
178. [178] Gobbi, L.T., et al. Exercise programs improve mobility and balance in people with Parkinson's disease. Park. Relat. Disord. 15:Suppl 3 (2009), S49–S52.
179. [179] Li, F., et al. Tai chi and postural stability in patients with Parkinson's disease. N. Engl. J. Med. 366:6 (2012), 511–519.
180. [180] Lau, Y.S., et al. Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson's disease with moderate neurodegeneration. Eur. J. Neurosci. 33:7 (2011), 1264–1274.
181. [181] Yoon, M.C., et al. Treadmill exercise suppresses nigrostriatal dopaminergic neuronal loss in 6-hydroxydopamine-induced Parkinson's rats. Neurosci. Lett. 423:1 (2007), 12–17.
182. [182] Tuon, T., et al. Physical training exerts neuroprotective effects in the regulation of neurochemical factors in an animal model of Parkinson's disease. Neuroscience 227 (2012), 305–312.
183. [183] Maswood, N., et al. Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson's disease. Proc. Natl. Acad. Sci. USA 101:52 (2004), 18171–18176.
184. [184] Vanitallie, T.B., et al. Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study. Neurology 64:4 (2005), 728–730.
185. [185] Tieu, K., et al. D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. J. Clin. Invest. 112:6 (2003), 892–901.
186. [186] Kashiwaya, Y., et al. D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease. Proc. Natl. Acad. Sci. USA 97:10 (2000), 5440–5444.
187. [187] Imamura, K., et al. D-beta-hydroxybutyrate protects dopaminergic SH-SY5Y cells in a rotenone model of Parkinson's disease. J. Neurosci. Res. 84:6 (2006), 1376–1384.
188. [188] Evans, J.R., Barker, R.A., Neurotrophic factors as a therapeutic target for Parkinson's disease. Expert Opin. Ther. Targets 12:4 (2008), 437–447.
189. [189] Kim, W., Egan, J.M., The role of incretins in glucose homeostasis and diabetes treatment. Pharmacol. Rev. 60:4 (2008), 470–512.
190. [190] Mattson, M.P., Perry, T., Greig, N.H., Learning from the gut. Nat. Med. 9:9 (2003), 1113–1115.
191. [191] Harkavyi, A., et al. Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson's disease. J. Neuroinflamm., 5, 2008, 19.
192. [192] Li, Y., et al. GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism. Proc. Natl. Acad. Sci. USA 106:4 (2009), 1285–1290.
193. [193] Liu, W., et al. Neuroprotective effects of lixisenatide and liraglutide in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. Neuroscience 303 (2015), 42–50.
194. [194] Foltynie, T., Aviles-Olmos, I., Exenatide as a potential treatment for patients with Parkinson's disease: first steps into the clinic. Alzheimers Dement. 10:1 Suppl (2014), S38–S46.
195. [195] Bruce-Keller, A.J., et al. Food restriction reduces brain damage and improves behavioral outcome following excitotoxic and metabolic insults. Ann. Neurol. 45:1 (1999), 8–15.
196. [196] Duan, W., et al. Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice. Proc. Natl. Acad. Sci. USA 100:5 (2003), 2911–2916.
197. [197] Potter, M.C., et al. Exercise is not beneficial and may accelerate symptom onset in a mouse model of Huntington's disease. PLoS Curr., 2, 2010 (p. Rrn1201).
198. [198] Ruskin, D.N., et al. A ketogenic diet delays weight loss and does not impair working memory or motor function in the R6/2 1J mouse model of Huntington's disease. Physiol. Behav. 103:5 (2011), 501–507.
199. [199] Martin, B., et al. Exendin-4 improves glycemic control, ameliorates brain and pancreatic pathologies, and extends survival in a mouse model of Huntington's disease. Diabetes 58:2 (2009), 318–328.
200. [200] Wrann, C.D., et al. Exercise induces hippocampal BDNF through a PGC-1alpha/FNDC5 pathway. Cell Metab. 18:5 (2013), 649–659.
201. [201] Moon, H.Y., et al. Running-induced systemic cathepsin B secretion is associated with memory function. Cell Metab. 24:2 (2016), 332–340.
202. [202] Ng, M., et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global burden of disease study 2013. Lancet 384:9945 (2014), 766–781.
203. [203] Guo, Z.H., Mattson, M.P., In vivo 2-deoxyglucose administration preserves glucose and glutamate transport and mitochondrial function in cortical synaptic terminals after exposure to amyloid beta-peptide and iron: evidence for a stress response. Exp. Neurol. 166:1 (2000), 173–179.
204. [204] Johnson, S.C., et al. mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Science 342:6165 (2013), 1524–1528.
205. [205] Brown, K.D., et al. Activation of SIRT3 by the NAD(+) precursor nicotinamide riboside protects from noise-induced hearing loss. Cell Metab. 20:6 (2014), 1059–1068.