<strong>小分子化合物影响神经干细胞再生的思考</strong>

摘要/Abstract

摘要：近年来有不少研究兴趣聚焦于基于神经干细胞治疗阿尔茨海默病（Alzheimer’s disease，AD）等神经退行性疾病的策略。到目前为止，所谓的再生医学主要集中于用多能胚胎干细胞进行细胞移植治疗。虽然已经有了一些令人激动的研究结果，但胚胎干细胞替代治疗仍然面临一些障碍，包括免疫排斥、突变带来的过度生长、伦理学争论等。代之而起的探索是用小分子化合物直接调制内源性干细胞的命运，已经取得一些结果，但许多涉及神经干细胞与局部小环境的相互作用及神经干细胞特异性信号机制的基础问题有待阐明。对这些问题的研究可能深化对神经干细胞生物学的认识，并促进创新性治疗药物的问世。

关键词:神经干细胞,阿尔茨海默病,小分子化合物,再生医学

Abstract:Recently， there is considerable interest in the development of stem cellbased strategies for the treatment of Alzheimer’s disease， one of the neurodegenerative diseases. To date， so-called regenerative approaches have focused mainly on the development of cell transplantation therapies using cells derived from pluripotent embryonic stem cells （ESCs）. Although some exciting preliminary reports have been described in regard of the efficacy of
ESC-derived replacement therapies， explorations involving ex vivo manipulated ESCs are hindered by events of mutation， immune rejection， and ethical controversy. An alternative approach involves direct in vivo modulation of endogenous adult stem cell populations using small molecules. Although many results have been reported， the interaction between neural stem cell and local niche and the specific signal mechanisms of neural stem cell remain to be
elucidated. Here we present the thinking of the chemical approaches to the regulation of neural stem cell biology that are yielding new biological insights and that may potentially lead to innovative new drugs.

Key words:neural stem cells,Alzheimer&,rsquo,s disease,small molecule,regenerative medicine

中图分类号:

R964

张力航，殷明.小分子化合物影响神经干细胞再生的思考[J]. 神经药理学报, 2017, 7(1): 1-9.

ZHANG Li-hang， YIN Ming.Thinking of Influences of Small Molecules on Neural Stem Cell Neurogenesis[J]. Acta Neuropharmacologica, 2017, 7(1): 1-9.

参考文献

[1] Prince Martin, Adelina Comas-Herrera, Martin Knapp, et al. World Alzheimer report 2016: improving healthcare for people living with dementia: coverage, quality and costs now and in the future [R]. London: Alzheimer’s Disease International (ADI), 2016: 84-104.

[2] De Strooper Bart, Eric Karran. The cellular phase of Alzheimer’s disease [J]. Cell, 2016, 164(4): 603-615.

[3]Jeffrey Cummings, Paul S Aisen, Bruno DuBois, et al. Drug development in Alzheimer’s disease: the path to 2025 [J]. Alzheimer's Research & Therapy, 2016, 8(1): 39.

[4] Shubham Misra, Bikash Medhi. Drug development status for Alzheimer’s disease: present scenario [J]. Neurol Sci, 2013, 34(6): 831–839.

[5] Kevin M Felsenstein, Kate M Candelario, Dennis A Steindler, et al. Regenerative medicine in Alzheimer’s disease [J]. Translational Research, 2014, 163(4): 432-438

[6] John Hardy, Dennis J Selkoe. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics [J]. Science, 2002， 297(5580):353-356.

[7] Maria Laura Giuffrida, Filippo Caraci, Bruno Pignataro, et al. Beta-amyloid monomers are neuroprotective [J]. J Neurosci, 2009, 29(34):10582-10587

[8] Olaf Bergmann, Jonas Frisén. Why adults need new brain cell [J]. Science, 2013, 340(6133): 695-670.

[9] Fiona Doetsch. A niche for adult neural stem cells [J]. Curr Opin Genet Dev, 2003, 13(5): 543-550.

[10] Roland Coras, Florian Siebzehnrubl, Elisabeth Pauli, et al. Low proliferation and differentiation capacities of adult hippocampal stem cells correlate with memory dysfunction in humans [J]. Brain, 2010, 133(11):3359-3372.

[11] Claudia Lieberwirth, Pan Yong-liang, Liu Yan, et al. Hippocampal adult neurogenesis: Its regulation and potential role in spatial learning and memory [J]. Brain Research, 2016 1644: 127-140.

[12] Tincer Gizem, Violeta Mashkaryan, Prabesh Bhattarai, et al. Focus: The Aging Brain: Neural stem/progenitor cells in Alzheimer’s disease[J]. J Yale of Biology and Medicine, 2016, 89(1): 23.

[13] Abdel-Salam OME. Stem cell therapy for Alzheimer’s disease [J]. CNS & Neurological Disorders-Drug Targets, 2011, 10(4):459-485.

[14] Chen Qian, Akira Nakajima, Se Hoon Choi, et al. Adult neurogenesis is functionally associated with AD-like neurodegeneration [J]. Neurobiol Dis, 2008, 29(2):316-326.

[15] He N, Jin Wei-lin, Lok Keng Hoe, et al. Amyloid-b1–42 oligomer accelerates senescence in adult hippocampal neural stem/progenitor cells via formylpeptide receptor 2 [J]. Cell Death and Disease, 2013, 4(11):e924.

[16] Jin Kun-lin, Alyson L Peel, Xiao ou Mao, et al. Increased hippocampal neurogenesis in Alzheimer’s disease [J]. PNAS 2004, 101(1):343-347.

[17] Iryna Ziabreva, Elaine Perry, Robert Perry, et al. Altered neurogenesis in Alzheimer’s disease [J]. J Psychosom Res, 2006, 61(3):311-316.

[18] Li Bin, Hidenaga Yamamori, Yoshitaka Tatebayashi, et al. Failure of neuronal maturation in Alzheimer disease dentate gyrus [J]. J Neuropathol Exp Neurol, 2008, 67(1):78-84.

[19] Wesley W Chen, Mathew Blurton-Jones. Concise review: can stem cells be used to tread or model Alzheimer’s disease? [J] Stem Cells, 2012, 30(12):2612-2618.

[20] Lee Ji Han, Il-Hoan Oh, Hyun Kook Lim. Stem Cell Therapy: A Prospective Treatment for Alzheimer's Disease [J]. Psychiatry Investigation, 2016, 13(6): 583-589.

[21] Dennis Steindler, Tareck Kadrie, Helen Fillmore, et al. The subepenedymal zone: “brain marrow” [J]. Prog Brain Res, 1996, 108: 349-363.

[22] Reynolds B A, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system [J]. Science, 1992, 255(5052):1707-1710.

[23] Dana Alliance Steindler, Pincus DW. Stem cells and neurogenesis in the adult human brain [J]. Lancet, 2002, 359(9311):1047-1054.

[24] Ivy S Samuels, J Colleen Karlo, Alicia N Faruzzi, et al. Deletion of ERK2 motogen-activated protein kinase identifies its key roles in cortical neurogenesis and cognitive function [J]. J Neurosci, 2008, 28(27):6983-6995.

[25] Zhang Chun-li, Zou Yu-hua, He Wei-min, et al. A role for adult TXL-positive neural stem cells in learning and behavior [J]. Nature, 2008, 451(7181):1004-1007.

[26] Malcolm Maden. Retinoic acid in the development, regeneration and maintenance of the nervous system [J].Nat Rev Neurosci, 2007, 8(10):755–765.

[27] Phedias Diamandis, Jan Wildenhain, Ian D Clarke, et al. Chemical genetics reveals a complex functional ground state of neural stem cells [J].Nat Chem Biol, 2007, 3(5):268–273

[28] Maria Frank-Kamenetsky, Zhang Xiao-yan, Steve Bottega, et al. Small-molecule modulators of Hedgehog signaling: identification and characterization of Smoothened agonists and antagonists [J]. J Biol, 2002, 1(2):10.

[29] Heiko Wurdak, Zhu Shou-tian, Kyung Hoon Min, et al. A small molecule accelerates neuronal differentiation in the adult rat [J]. Proc Natl Acad Sci, 2010, 107(38):16542–16547.

[30] Jonathan P Saxe, Wu Hao, Theresa K Kelly, et al. A phenotypic small-molecule screen identifies an orphan ligand-receptor pair that regulates neural stem cell differentiation [J].Chem Biol, 2007, 14(9):1019–1030.

[31] Canudas A M, Di Giorgi-Gerevini V, Iacovelli L, et al. PHCCC, a specific enhancer of type 4 metabotropic glutamate receptors, reduces proliferation and promotes differentiation of cerebellar granule cell neuroprecursors [J]. J Neurosci, 2004, 24(46):10343–10352.

[32] Cheng Lin, Gao Long-fei, Guan Wu-qiang, et al. Direct conversion of astrocytes into neuronal cells by drug cocktail [J]. Cell Research, 2015, 25(11): 1269

[33] Zhang Lei, Yin Jiu-chao, Hana Yeh, et al. Small molecules efficiently reprogram human astroglial cells into functional neurons [J].Cell Stem Cell, 2015, 17(6): 735-747.

[34] Gao Long-fei, Guan Wu-qiang, Wang Min, et al. Direct generation of human neuronal cells from adult astrocytes by small molecules [J]. Stem Cell Reports, 2017, 8(3): 538-547

[35] Carlos P Fitzsimons, Emma van Bodegraven, Marijn Schouten, et al. Epigenetic regulation of adult neural stem cells: implications for Alzheimer’s disease [J]. Molecular Neurodegeneration, 2014, 9(1): 25

[36] Shen Si-ming, Li Jia-dong, Patrizia Casaccia-Bonnefil. Histone modifications affect timing of oligodendrocyte progenitor differentiation in the developing rat brain [J]. J Cell Biol, 2005, 169(4):577–589

[37] Zhang Ling, Li Peng, Tiffany Hsu, et al. Small-molecule blocks malignant astrocyte proliferation and induces neuronal gene expression [J]. Differentiation, 2011, 81(4): 233-242

[38] Philippe Taupin. Neurogenic drugs and compounds [J]. Recent Pat CNS Drug Discov, 2010, 5(3):253-257.

[39] Ma Jing, Gao Yuan, Jiang Lin, et al. Fluoxetine attenuates the impairment of spatial learning ability and prevents neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer's disease mice[J]. Oncotarget, 2017, 8(17): 27676.

[40] Mowla A, Mosavinasab M, Pani A. Does fluxetine have any effect on the cognition of patients with mild cognitive impairment? A double-blind, placebo-controlled, clinical trial [J]. J Clin Psychopharmacol, 2007, 27(1):67-70.

[41] Juan Sanchez-Ramos, Cynthia R Cimino, Ross Avila, et al. Pilot study of granulocyte-colony stimulating factor for treatment of Alzheimer’s disease [J]. J Alzheimers Dis, 2012, 31(4):843-855.

[42] Keith Wollen. Alzheimer’s disease: the pros and cons of pharmaceutical, nutritional, botanical, and stimulatory therapies, with a discussion of treatment strategies from the perspective of patients and practitioners [J]. Altern Med Rev, 2010, 15(3):223-244.

[43] Robert J Williams, Jeremy PE Spencer. Flavonoids, cognition, and dementia: actions, mechanisms and potential therapeutics utility for Alzheimer’s disease [J]. Free Radic Biol, 2012, 52(1):35-45.

[44] Ren Zhi-li, Zuo Ping-ping. Neural regeneration: role of traditional Chinese medicine in neurological diseases treatment [J]. J Pharmacol Sci, 2012, 120(3):139-145.

[45] Florian T Merkle, Zaman Mirzadeh, Arturo Alvarez-Buylla. Mosaic organization of neural stem cells in the adult brain [J]. Science, 2007, 317(5836): 381–384.

[46] Alvarez-Buylla A, Daniel A Lim. For the long run: maintaining germinal niches in the adult brain [J]. Neuron, 2004, 41(5):683–686.

[47] Zhao Chun-mei, Deng Wei, Fred H Gage. Mechanisms and functional implications of adult neurogenesis [J]. Cell, 2008, 132(4): 645–660.

[48] Juan I Castrillo, Stephen G Oliver. Alzheimer’s as a systems-level disease involving the interplay of multiple cellular networks [J]. Systems Biology of Alzheimer's Disease, 2016: 3-48.

[49] Lyssiotis C A, Lairson L L, Boitano A E, et al. Chemical control of stem cell fate and developmental potential [J]. Angew Chem Int Ed Engl, 2011, 50(1):200–242.

[50] Andras J Bauer, Brent Stockwell. Neurobiological applications of small molecule screening [J]. Chem. Rev, 2008, 108(5):1774–1786.

小分子化合物影响神经干细胞再生的思考

Thinking of Influences of Small Molecules on Neural Stem Cell Neurogenesis

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