Targeting Nicotinamide Phosphoribosyltransferase as a Potential Therapeutic Strategy to Restore Adult Neurogenesis

CNS Neuroscience and Therapeutics

Volumn 22, Issue 6, 2016, Pages 431-439

  Wang, Shu Na ^a   Xu, Tian Ying ^a   Li, Wen Lin ^a   Miao, Chao Yu ^a,b  

^a SECOND MILITARY MEDICAL UNIVERSITY   (China)

^b BEIJING INSTITUTE FOR BRAIN DISORDERS   (China)

Author keywords

Adult neurogenesis; Neurological disease; Nicotinamide adenine dinucleotide; Nicotinamide mononucleotide; Nicotinamide phosphoribosyltransferase

Indexed keywords

CARBAZOLE DERIVATIVE; NEUROPROTECTIVE AGENT; NICOTINAMIDE ADENINE DINUCLEOTIDE; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; P7C3; P7C3 A20; P7C3 S243; UNCLASSIFIED DRUG; NICOTINAMIDE NUCLEOTIDE;

ADULT; ADULTHOOD; AGING; AMYOTROPHIC LATERAL SCLEROSIS; BRAIN ISCHEMIA; CEREBROVASCULAR ACCIDENT; DEGENERATIVE DISEASE; DEPRESSION; DOWN SYNDROME; DRUG METABOLISM; DRUG TARGETING; ENZYME ACTIVITY; HUMAN; NERVE INJURY; NERVOUS SYSTEM DEVELOPMENT; NEURAL STEM CELL; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; REVIEW; STRUCTURE ACTIVITY RELATION; SUBVENTRICULAR ZONE; TRAUMATIC BRAIN INJURY; ANIMAL; DRUG EFFECTS; ENZYMOLOGY; METABOLISM; NERVOUS SYSTEM DISEASES; PHYSIOLOGY;

AGING; ANIMALS; HUMANS; NAD; NERVOUS SYSTEM DISEASES; NEUROGENESIS; NICOTINAMIDE MONONUCLEOTIDE; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE;

EID: 84962263596     PISSN: 17555930     EISSN: 17555949     Source Type: Journal    
DOI: 10.1111/cns.12539     Document Type: Review

References (111)

1. Altman J, Das GD. Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 1965;124:319-335.
2. Eriksson PS, Perfilieva E, Bjork-Eriksson T, et al. Neurogenesis in the adult human hippocampus. Nat Med 1998;4:1313-1317.
3. Jessberger S, Gage FH. Adult neurogenesis: Bridging the gap between mice and humans. Trends Cell Biol 2014;24:558-563.
4. Alvarez-Buylla A, Lim DA. For the long run: Maintaining germinal niches in the adult brain. Neuron 2004;41:683-686.
5. Zhao C, Deng W, Gage FH. Mechanisms and functional implications of adult neurogenesis. Cell 2008;132:645-660.
6. Spalding KL, Bergmann O, Alkass K, et al. Dynamics of hippocampal neurogenesis in adult humans. Cell 2013;153:1219-1227.
7. Bergmann O, Liebl J, Bernard S, et al. The age of olfactory bulb neurons in humans. Neuron 2012;74:634-639.
8. Bergmann O, Spalding KL, Frisen J. Adult neurogenesis in humans. Cold Spring Harb Perspect Biol 2015;7:a018994.
9. Ben Abdallah NM, Slomianka L, Vyssotski AL, Lipp HP. Early age-related changes in adult hippocampal neurogenesis in C57 mice. Neurobiol Aging 2010;31:151-161.
10. Jin K, Sun Y, Xie L, et al. Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice. Aging Cell 2003;2:175-183.
11. Lugert S, Basak O, Knuckles P, et al. Quiescent and active hippocampal neural stem cells with distinct morphologies respond selectively to physiological and pathological stimuli and aging. Cell Stem Cell 2010;6:445-456.
12. Decker L, Picard-Riera N, Lachapelle F, Baron-Van Evercooren A. Growth factor treatment promotes mobilization of young but not aged adult subventricular zone precursors in response to demyelination. J Neurosci Res 2002;69:763-771.
13. Moraga A, Pradillo JM, Garcia-Culebras A, et al. Aging increases microglial proliferation, delays cell migration, and decreases cortical neurogenesis after focal cerebral ischemia. J Neuroinflammation 2015;12:87.
14. Jin K, Minami M, Lan JQ, et al. Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci USA 2001;98:4710-4715.
15. Jin K, Wang X, Xie L, et al. Evidence for stroke-induced neurogenesis in the human brain. Proc Natl Acad Sci USA 2006;103:13198-13202.
16. Kim DH, Lee HE, Kwon KJ, et al. Early immature neuronal death initiates cerebral ischemia-induced neurogenesis in the dentate gyrus. Neuroscience 2015;284:42-54.
17. Chirumamilla S, Sun D, Bullock MR, Colello RJ. Traumatic brain injury induced cell proliferation in the adult mammalian central nervous system. J Neurotrauma 2002;19:693-703.
18. Rice A. Proliferation and neuronal differentiation of mitotically active cells following traumatic brain injury. Exp Neurol 2003;183:406-417.
19. Dash PK, Mach SA, Moore AN. Enhanced neurogenesis in the rodent hippocampus following traumatic brain injury. J Neurosci Res 2001;63:313-319.
20. Agosta F, Weiler M, Filippi M. Propagation of pathology through brain networks in neurodegenerative diseases: From molecules to clinical phenotypes. CNS Neurosci Ther 2015;21:754-767.
21. Jabir NR, Firoz CK, Baeesa SS, et al. Synopsis on the linkage of Alzheimer's and Parkinson's disease with chronic diseases. CNS Neurosci Ther 2015;21:1-7.
22. Camilleri A, Vassallo N. The centrality of mitochondria in the pathogenesis and treatment of Parkinson's disease. CNS Neurosci Ther 2014;20:591-602.
23. Boekhoorn K, Joels M, Lucassen PJ. Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus. Neurobiol Dis 2006;24:1-14.
24. Curtis MA, Penney EB, Pearson AG, et al. Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain. Proc Natl Acad Sci USA 2003;100:9023-9027.
25. Scharfman HE, Hen R. Neuroscience. Is more neurogenesis always better? Science 2007;315:336-338.
26. Peng GP, Feng Z, He FP, et al. Correlation of hippocampal volume and cognitive performances in patients with either mild cognitive impairment or Alzheimer's disease. CNS Neurosci Ther 2015;21:15-22.
27. Hoglinger GU, Rizk P, Muriel MP, et al. Dopamine depletion impairs precursor cell proliferation in Parkinson disease. Nat Neurosci 2004;7:726-735.
28. O'Keeffe GC, Tyers P, Aarsland D, Dalley JW, Barker RA, Caldwell MA. Dopamine-induced proliferation of adult neural precursor cells in the mammalian subventricular zone is mediated through EGF. Proc Natl Acad Sci USA 2009;106:8754-8759.
29. Mezey E, Dehejia A, Harta G, Papp MI, Polymeropoulos MH, Brownstein MJ. Alpha synuclein in neurodegenerative disorders: Murderer or accomplice? Nat Med 1998;4:755-757.
30. Goedert M. Alpha-synuclein and neurodegenerative diseases. Nat Rev Neurosci 2001;2:492-501.
31. Winner B, Regensburger M, Schreglmann S, et al. Role of alpha-synuclein in adult neurogenesis and neuronal maturation in the dentate gyrus. J Neurosci 2012;32:16906-16916.
32. Spalding KL, Bhardwaj RD, Buchholz BA, Druid H, Frisen J. Retrospective birth dating of cells in humans. Cell 2005;122:133-143.
33. Ernst A, Alkass K, Bernard S, et al. Neurogenesis in the striatum of the adult human brain. Cell 2014;156:1072-1083.
34. Tang YH, Ma YY, Zhang ZJ, Wang YT, Yang GY. Opportunities and challenges: Stem cell-based therapy for the treatment of ischemic stroke. CNS Neurosci Ther 2015;21:337-347.
35. Chen J, Leak RK, Yang GY. Perspective for stroke and brain injury research: Mechanisms and potential therapeutic targets. CNS Neurosci Ther 2015;21:301-303.
36. Zhu Y, Guan YM, Huang HL, Wang QS. Human umbilical cord blood mesenchymal stem cell transplantation suppresses inflammatory responses and neuronal apoptosis during early stage of focal cerebral ischemia in rabbits. Acta Pharmacol Sin 2014;35:585-591.
37. Tripathy D, Verma P, Nthenge-Ngumbau DN, Banerjee M, Mohanakumar KP. Regenerative therapy in experimental Parkinsonism: Mixed population of differentiated mouse embryonic stem cells, rather than magnetically sorted and enriched dopaminergic cells provide neuroprotection. CNS Neurosci Ther 2014;20:717-727.
38. Preiss J, Handler P. Enzymatic synthesis of nicotinamide mononucleotide. J Biol Chem 1957;225:759-770.
39. Siderovski DP, Blum S, Forsdyke RE, Forsdyke DR. A set of human putative lymphocyte G0/G1 switch genes includes genes homologous to rodent cytokine and zinc finger protein-encoding genes. DNA Cell Biol 1990;9:579-587.
40. Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I. Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol Cell Biol 1994;14:1431-1437.
41. Martin PR, Shea RJ, Mulks MH. Identification of a plasmid-encoded gene from Haemophilus ducreyi which confers NAD independence. J Bacteriol 2001;183:1168-1174.
42. Rongvaux A, Shea RJ, Mulks MH, et al. Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis. Eur J Immunol 2002;32:3225-3234.
43. Ramsey KM, Yoshino J, Brace CS, et al. Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science 2009;324:651-654.
44. Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P. Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science 2009;324:654-657.
45. Zhao Y, Liu XZ, Tian WW, Guan YF, Wang P, Miao CY. Extracellular visfatin has nicotinamide phosphoribosyltransferase enzymatic activity and is neuroprotective against ischemic injury. CNS Neurosci Ther 2014;20:539-547.
46. Jing Z, Xing J, Chen X, et al. Neuronal NAMPT is released after cerebral ischemia and protects against white matter injury. J Cereb Blood Flow Metab 2014;34:1613-1621.
47. Zhao Y, Guan YF, Zhou XM, et al. Regenerative neurogenesis after ischemic stroke promoted by nicotinamide phosphoribosyltransferase-nicotinamide adenine dinucleotide cascade. Stroke 2015;46:1966-1974.
48. Kitani T, Okuno S, Fujisawa H. Growth phase-dependent changes in the subcellular localization of pre-B-cell colony-enhancing factor11The nucleotide sequence of cDNA for rat PBEF has been submitted to the DDBJ/EMBL/GenBank under the accession number AB081730. FEBS Lett 2003;544:74-78.
49. Revollo JR, Korner A, Mills KF, et al. Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab 2007;6:363-375.
50. Yang H, Yang T, Baur JA, et al. Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell 2007;130:1095-1107.
51. Pittelli M, Formentini L, Faraco G, et al. Inhibition of nicotinamide phosphoribosyltransferase: Cellular bioenergetics reveals a mitochondrial insensitive NAD pool. J Biol Chem 2010;285:34106-34114.
52. Garten A, Schuster S, Penke M, Gorski T, de Giorgis T, Kiess W. Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nat Rev Endocrinol 2015;11:535-546.
53. Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol 2014;24:464-471.
54. Revollo JR, Grimm AA, Imai S. The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem 2004;279:50754-50763.
55. Bowlby SC, Thomas MJ, D'Agostino RB, Kridel SJ. Nicotinamide phosphoribosyl transferase (Nampt) is required for de novo lipogenesis in tumor cells. PLoS One 2012;7:e40195.
56. Rodgers JT, Lerin C, Gerhart-Hines Z, Puigserver P. Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Lett 2008;582:46-53.
57. Bruzzone S, Fruscione F, Morando S, et al. Catastrophic NAD+ depletion in activated T lymphocytes through Nampt inhibition reduces demyelination and disability in EAE. PLoS One 2009;4:e7897.
58. Koltai E, Szabo Z, Atalay M, et al. Exercise alters SIRT1, SIRT6, NAD and NAMPT levels in skeletal muscle of aged rats. Mech Ageing Dev 2010;131:21-28.
59. Van Gool F, Galli M, Gueydan C, et al. Intracellular NAD levels regulate tumor necrosis factor protein synthesis in a sirtuin-dependent manner. Nat Med 2009;15:206-210.
60. Pillai JB, Isbatan A, Imai S, Gupta MP. Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity. J Biol Chem 2005;280:43121-43130.
61. van der Horst A, Tertoolen LG, de Vries-Smits LM, Frye RA, Medema RH, Burgering BM. FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1). J Biol Chem 2004;279:28873-28879.
62. Bordone L, Motta MC, Picard F, et al. Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells. PLoS Biol 2006;4:e31.
63. Luo X, Kraus WL. On PAR with PARP: Cellular stress signaling through poly(ADP-ribose) and PARP-1. Genes Dev 2012;26:417-432.
64. Song J, Ke SF, Zhou CC, et al. Nicotinamide phosphoribosyltransferase is required for the calorie restriction-mediated improvements in oxidative stress, mitochondrial biogenesis, and metabolic adaptation. J Gerontol A Biol Sci Med Sci 2014;69:44-57.
65. Folmes CD, Dzeja PP, Nelson TJ, Terzic A. Metabolic plasticity in stem cell homeostasis and differentiation. Cell Stem Cell 2012;11:596-606.
66. Wang P, Miao CY. NAMPT as a therapeutic target against stroke. Trends Pharmacol Sci 2015;36:891-905.
67. Stein LR, Imai S. Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging. EMBO J 2014;33:1321-1340.
68. Zhang W, Xie Y, Wang T, et al. Neuronal protective role of PBEF in a mouse model of cerebral ischemia. J Cereb Blood Flow Metab 2010;30:1962-1971.
69. Wang P, Xu TY, Guan YF, et al. Nicotinamide phosphoribosyltransferase protects against ischemic stroke through SIRT1-dependent adenosine monophosphate-activated kinase pathway. Ann Neurol 2011;69:360-374.
70. Yoon MJ, Yoshida M, Johnson S, et al. SIRT1-Mediated eNAMPT Secretion from Adipose Tissue Regulates Hypothalamic NAD+ and Function in Mice. Cell Metab 2015;21:706-717.
71. Wang P, Xu TY, Guan YF, Su DF, Fan GR, Miao CY. Perivascular adipose tissue-derived visfatin is a vascular smooth muscle cell growth factor: Role of nicotinamide mononucleotide. Cardiovasc Res 2009;81:370-380.
72. Miao CY, Li ZY. The role of perivascular adipose tissue in vascular smooth muscle cell growth. Br J Pharmacol 2012;165:643-658.
73. Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab 2011;14:528-536.
74. Karamanlidis G, Lee CF, Garcia-Menendez L, et al. Mitochondrial complex I deficiency increases protein acetylation and accelerates heart failure. Cell Metab 2013;18:239-250.
75. Gomes AP, Price NL, Ling AJ, et al. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 2013;155:1624-1638.
76. Mouchiroud L, Houtkooper RH, Moullan N, et al. The NAD(+)/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell 2013;154:430-441.
77. Chang HC, Guarente L. SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell 2013;153:1448-1460.
78. Satoh A, Stein L, Imai S. The role of mammalian sirtuins in the regulation of metabolism, aging, and longevity. Handb Exp Pharmacol 2011;206:125-162.
79. Wang P, Vanhoutte PM, Miao CY. Visfatin and cardio-cerebro-vascular disease. J Cardiovasc Pharmacol 2012;59:1-9.
80. Alano CC, Garnier P, Ying W, Higashi Y, Kauppinen TM, Swanson RA. NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal death. J Neurosci 2010;30:2967-2978.
81. Bi J, Li H, Ye SQ, Ding S. Pre-B-cell colony-enhancing factor exerts a neuronal protection through its enzymatic activity and the reduction of mitochondrial dysfunction in in vitro ischemic models. J Neurochem 2012;120:334-346.
82. Wang S, Xing Z, Vosler PS, et al. Cellular NAD replenishment confers marked neuroprotection against ischemic cell death: Role of enhanced DNA repair. Stroke 2008;39:2587-2595.
83. Erfani S, Khaksari M, Oryan S, Shamsaei N, Aboutaleb N, Nikbakht F. Nampt/PBEF/visfatin exerts neuroprotective effects against ischemia/reperfusion injury via modulation of Bax/Bcl-2 ratio and prevention of caspase-3 activation. J Mol Neurosci 2015;56:237-243.
84. Erfani S, Khaksari M, Oryan S, et al. Visfatin reduces hippocampal CA1 cells death and improves learning and memory deficits after transient global ischemia/reperfusion. Neuropeptides 2015;49:63-68.
85. Erfani S, Aboutaleb N, Oryan S, et al. Visfatin inhibits apoptosis and necrosis of hippocampus CA3 cells following transient global ischemia/reperfusion in rats. Int J Pep Res Ther 2015;21:223-228.
86. Zheng C, Han J, Xia W, Shi S, Liu J, Ying W. NAD(+) administration decreases ischemic brain damage partially by blocking autophagy in a mouse model of brain ischemia. Neurosci Lett 2012;512:67-71.
87. Wang P, Guan YF, Du H, Zhai QW, Su DF, Miao CY. Induction of autophagy contributes to the neuroprotection of nicotinamide phosphoribosyltransferase in cerebral ischemia. Autophagy 2012;8:77-87.
88. Wang P, Li WL, Liu JM, Miao CY. NAMPT and NAMPT-controlled NAD metabolism in vascular repair. J Cardiovasc Pharmacol 2015. DOI: 10.1097/FJC.0000000000000332 [Epub ahead of print].
89. Wang P, Guan YF, Li WL, Lu GC, Liu JM, Miao CY. Nicotinamide phosphoribosyltransferase facilitates post-stroke angiogenesis. CNS Neurosci Ther 2015;21:475-477.
90. Lovren F, Pan Y, Shukla PC, et al. Visfatin activates eNOS via Akt and MAP kinases and improves endothelial cell function and angiogenesis in vitro and in vivo: Translational implications for atherosclerosis. Am J Physiol Endocrinol Metab 2009;296:E1440-E1449.
91. Wang P, Du H, Zhou CC, et al. Intracellular NAMPT-NAD+-SIRT1 cascade improves post-ischaemic vascular repair by modulating Notch signalling in endothelial progenitors. Cardiovasc Res 2014;104:477-488.
92. Xu TY, Zhang SL, Dong GQ, et al. Discovery and characterization of novel small-molecule inhibitors targeting nicotinamide phosphoribosyltransferase. Sci Rep 2015;5:10043.
93. Wang X, Xu TY, Liu XZ, et al. Discovery of novel inhibitors and fluorescent probe targeting NAMPT. Sci Rep 2015;5:12657.
94. Sampath D, Zabka TS, Misner DL, O'Brien T, Dragovich PS. Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) as a therapeutic strategy in cancer. Pharmacol Ther 2015;151:16-31.
95. Wang G, Han T, Nijhawan D, et al. P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage. Cell 2014;158:1324-1334.
96. Pieper AA, Xie S, Capota E, et al. Discovery of a proneurogenic, neuroprotective chemical. Cell 2010;142:39-51.
97. Naidoo J, De Jesus-Cortes H, Huntington P, et al. Discovery of a neuroprotective chemical, (S)-N-(3-(3, 6-dibromo-9H-carbazol-9-yl)-2-fluoropropyl)-6-methoxypyridin-2-amine [(-)-P7C3-S243], with improved druglike properties. J Med Chem 2014;57:3746-3754.
98. MacMillan KS, Naidoo J, Liang J, et al. Development of proneurogenic, neuroprotective small molecules. J Am Chem Soc 2011;133:1428-1437.
99. Yoon HJ, Kong SY, Park MH, et al. Aminopropyl carbazole analogues as potent enhancers of neurogenesis. Bioorg Med Chem 2013;21:7165-7174.
100. Erbel-Sieler C, Dudley C, Zhou Y, et al. Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors. Proc Natl Acad Sci USA 2004;101:13648-13653.
101. Pieper AA, Wu X, Han TW, et al. The neuronal PAS domain protein 3 transcription factor controls FGF-mediated adult hippocampal neurogenesis in mice. Proc Natl Acad Sci USA 2005;102:14052-14057.
102. De Jesus-Cortes H, Xu P, Drawbridge J, et al. Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of Parkinson disease. Proc Natl Acad Sci USA 2012;109:17010-17015.
103. Shin JY, Kong SY, Yoon HJ, Ann J, Lee J, Kim HJ. An aminopropyl carbazole derivative induces neurogenesis by increasing final cell division in neural stem cells. Biomol Ther (Seoul) 2015;23:313-319.
104. Blaya MO, Bramlett HM, Naidoo J, Pieper AA, Dietrich WD. Neuroprotective efficacy of a proneurogenic compound after traumatic brain injury. J Neurotrauma 2014;31:476-486.
105. Yin TC, Britt JK, De Jesus-Cortes H, et al. P7C3 neuroprotective chemicals block axonal degeneration and preserve function after traumatic brain injury. Cell Rep 2014;8:1731-1740.
106. Kemp SW, Szynkaruk M, Stanoulis KN, et al. Pharmacologic rescue of motor and sensory function by the neuroprotective compound P7C3 following neonatal nerve injury. Neuroscience 2015;284:202-216.
107. Latchney SE, Jaramillo TC, Rivera PD, Eisch AJ, Powell CM. Chronic P7C3 treatment restores hippocampal neurogenesis. Neurosci Lett 2015;591:86-92.
108. Walker AK, Rivera PD, Wang Q, et al. The P7C3 class of neuroprotective compounds exerts antidepressant efficacy in mice by increasing hippocampal neurogenesis. Mol Psychiatry 2015;20:500-508.
109. Tesla R, Wolf HP, Xu P, et al. Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 2012;109:17016-17021.
110. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131:861-872.
111. Lancaster MA, Renner M, Martin CA, et al. Cerebral organoids model human brain development and microcephaly. Nature 2013;501:373-379.