Abstract：Neuron is the basic structure and functional unit of nervous system. Once the neurons are damaged or lost, the balance of neuroregulation will be destroyed and a series of nervous system diseases will be induced. Parkinson′s disease (PD) is a kind of chronic neurodegenerative disease caused by selective loss of many dopaminergic neurons in the dense region of the substantia nigra in the ventral midbrain. At present, conventional drugs and adjuvant therapies can only relieve clinical symptoms to a certain extent, but cannot fundamentally delay the progress of the disease. With the rapid development of stem cells and reprogramming technologies around the world, cell transplantation to deal with neurodegenerative diseases including Parkinson′s disease has become a new and potential therapy. This paper mainly summarizes the molecular mechanisms of Parkinson′s disease, the preparation of autogenous dopaminergic neurons and the research progresses of dopaminergic neurons transplantation in the treatment of Parkinson′s disease.
HASEGAWA T, KOBAYASHI J, ISHIYAMA S. Emerging disease-modifying strategies targeting alpha-synuclein in Parkinson′s disease[J]. Brain Nerve, 2020, 72(2): 143-150.
[2]
KLEIN C, WESTENBERGER A. Genetics of Parkinson′s disease[J]. Cold Spring Harb Perspect Med, 2012, 2(1):doi:10.110/cshperspect.a008888.
[3]
GE P, DAWSON V L, DAWSON T M. PINK1 and parkin mitochondrial quality control: a source of regional vulnerability in Parkinson′s disease [J]. Mol Neurodegener, 2020, 15(1): 20.
[4]
MOHAN KRISHNA G, ELANGO P, BHASKAR L V K S. Current therapeutic strategies and perspectives for neuroprotection in Parkinson′s disease[J]. Curr Pharm De, 2020, 26: 1-9.
[5]
LUO S, DU L, CUI Y. Potential therapeutic applications and developments of exosomes in Parkinson′s disease[J]. Mol Pharm, 2020, 17(5): 1447-1457.
[6]
BARKER R A, BARRETT J, MASON S L, et al. Fetal dopaminergic transplantation trials and the future of neural grafting in Parkinson′s disease [J]. Lancet Neurol, 2013, 12(1):84-91.
[7]
HEMMATI-DINARVAND M, SAEDI S, VALILO M, et al. Oxidative stress and Parkinson′s disease: conflict of oxidant-antioxidant systems[J]. Neurosci Lett, 2019, 709:134296.
[8]
WENG M, XIE X, LIU C, et al. The sources of reactive oxygen species and its possible role in the pathogenesis of Parkinson′s disease[J]. Parkinsons Dis, 2018, 2018:9163040.
[9]
JIANG Y, LIU J, CHEN L, et al. Serum secreted miR-137-containing exosomes affects oxidative stress of neurons by regulating OXR1 in Parkinson′s disease[J]. Brain Res, 2019, 1722:146331.
[10]
ZHANG Y, TAN F, XU P, et al. Recent advance in the relationship between excitatory amino acid transporters and Parkinson′s disease[J]. Neural Plast, 2016, 2016:8941327.
[11]
MEADE R M, FAIRLIE D P, MASON J M. Alpha-synuclein structure and Parkinson′s disease- lessons and emerging principles[J]. Mol Neurodegener, 2019, 14(1):29.
[12]
LUDTMANN M H R, ANGELOVA P R, HORROCKS M H, et al. Alpha-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson′s disease[J]. Nat Commun, 2018, 9(1):2293.
[13]
NGUYEN M, WONG Y C, YSSELSTEIN D, et al. Synaptic, mitochondrial, and lysosomal dysfunction in Parkinson′s disease[J]. Trends Neurosci, 2019, 42(2):140-149.
[14]
DIAS V, JUNN E, MOURADIAN M M. The role of oxidative stress in Parkinson′s disease[J]. J Parkinsons Dis, 2013, 3(4):461-491.
[15]
BURBULLA L F, SONG P, MAZZULLI J R, et al. Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson′s disease[J]. Science, 2017, 357(6357): 1255-1261.
[16]
ZHU J, DOU S, JIANG Y, et al. Apelin-13 protects dopaminergic neurons in MPTP-induced Parkinson′s disease model mice through inhibiting endoplasmic reticulum stress and promoting autophagy[J]. Brain Res, 2019, 1715: 203-212.
[17]
ZHU Y L, SUN M F, JIA X B, et al. Neuroprotective effects of astilbin on MPTP-induced Parkinson′s disease mice: glial reaction, alpha-synuclein expression and oxidative stress[J]. Int Immunopharmacol, 2019, 66: 19-27.
[18]
GUNAYDIN C, AVCI B, BOZKURT A, et al. Effects of agomelatine in rotenone-induced Parkinson′s disease in rats[J]. Neurosci Lett, 2019, 699: 71-76.
[19]
BOVE C, COLEMAN F H, TRAVAGLI R A. Characterization of the basic membrane properties of neurons of the rat dorsal motor nucleus of the vagus in paraquat-induced models of Parkinsonism[J]. Neuroscience, 2019, 418: 122-132.
[20]
HOU L, SUN F, SUN W, et al. Lesion of the locus coeruleus damages learning and memory performance in paraquat and maneb-induced mouse Parkinson′s disease model[J]. Neuroscience, 2019, 419: 129-140.
[21]
CASARRUBEA M, DI GIOVANNI G, CRESCIMANNO G, et al. Effects of substantia nigra pars compacta lesion on the behavioral sequencing in the 6-OHDA model of Parkinson′s disease[J]. Behav Brain Res, 2019, 362: 28-35.
[22]
BONATO J M, BASSANI T B, MILANI H, et al. Pioglitazone reduces mortality, prevents depressive-like behavior, and impacts hippocampal neurogenesis in the 6-OHDA model of Parkinson′s disease in rats [J]. Exp Neurol, 2018, 300: 188-200.
[23]
VIREL A, DUDKA I, LATERVEER R, et al. 1H-NMR profiling of the 6-OHDA parkinsonian rat brain reveals metabolic alterations and signs of recovery after N-acetylcysteine treatment[J]. Mol Cell Neurosci, 2019, 98: 131-139.
[24]
BURRE J. The synaptic function of alpha-synuclein[J]. J Parkinsons Dis, 2015, 5(4): 699-713.
[25]
LUNATI A, LESAGE S, BRICE A. The genetic landscape of Parkinson′s disease[J]. Rev Neurol, 2018, 174(9): 628-643.
[26]
PARMAR M, GREALISH S, HENCHCLIFFE C. The future of stem cell therapies for Parkinson′s disease[J]. Nat Rev Neurosci, 2020, 21(2): 103-115.
[27]
KIM J, SU S C, WANG H, et al. Functional integration of dopaminergic neurons directly converted from mouse fibroblasts[J]. Cell Stem Cell, 2011, 9(5): 413-419.
[28]
XU Z, CHU X, JIANG H, et al. Induced dopaminergic neurons: a new promise for Parkinson′s disease[J]. Redox Biol, 2017, 11: 606-612.
[29]
LIAO J, WU Z, WANG Y, et al. Enhanced efficiency of generating induced pluripotent stem (iPS) cells from human somatic cells by a combination of six transcription factors[J]. Cell Res, 2008, 18(5): 600-603.
[30]
KIM Y, KANG K, LEE S B, et al. Small molecule-mediated reprogramming of human hepatocytes into bipotent progenitor cells[J]. J Hepatol, 2019, 70(1): 97-107.
[31]
ZHAO Y. Chemically induced cell fate reprogramming and the acquisition of plasticity in somatic cells[J]. Curr Opin Chem Biol, 2019, 51: 146-153.
[32]
LI X, XU J, DENG H. Small molecule-induced cellular fate reprogramming: promising road leading to Rome[J]. Curr Opin Genet Dev, 2018, 52: 29-35.
[33]
HOU P, LI Y, ZHANG X, et al. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds[J]. Science, 2013, 341(6146): 651-654.
[34]
ZHAO Y, ZHAO T, GUAN J, et al. A XEN-like state bridges somatic cells to pluripotency during chemical reprogramming[J]. Cell, 2015, 163(7): 1678-1691.
[35]
YANG Y, LIU B, XU J, et al. Derivation of pluripotent stem cells with in vivo embryonic and extraembryonic Potency[J]. Cell, 2017, 169(2): 243-257.
[36]
PERRIER A L, TABAR V, BARBERI T, et al. Derivation of midbrain dopamine neurons from human embryonic stem cells[J]. Proc Natl Acad Sci USA, 2004, 101(34): 12543-12548.
[37]
THEKA I, CAIAZZO M, DVORETSKOVA E, et al. Rapid generation of functional dopaminergic neurons from human induced pluripotent stem cells through a single-step procedure using cell lineage transcription factors[J]. Stem Cells Transl Med, 2013, 2(6): 473-479.
[38]
COOPER O, HARGUS G, DELEIDI M, et al. Differentiation of human ES and Parkinson′s disease iPS cells into ventral midbrain dopaminergic neurons requires a high activity form of SHH, FGF8a and specific regionalization by retinoic acid[J]. Mol Cell Neurosci, 2010, 45(3): 258-266.
[39]
YAVARPOUR-BALI H, GHASEMI-KASMAN M, SHOJAEI A. Direct reprogramming of terminally differentiated cells into neurons: a novel and promising strategy for Alzheimer′s disease treatment[J]. Prog Neuropsychopharmacol Biol Psychiatr, 2020, 98: 109820.
[40]
YANG Y, CHEN R, WU X, et al. Rapid and efficient conversion of human fibroblasts into functional neurons by small molecules[J]. Stem Cell Reports, 2019, 13(5): 862-876.
[41]
PFISTERER U, KIRKEBY A, TORPER O, et al. Direct conversion of human fibroblasts to dopaminergic neurons[J]. Proc Natl Acad Sci USA, 2011, 108(25): 10343-10348.
[42]
CAIAZZO M, DELL′ANNO M T, DVORETSKOVA E, et al. Direct generation of functional dopaminergic neurons from mouse and human fibroblasts[J]. Nature, 2011, 476(7359): 224-227.
[43]
HARGUS G, COOPER O, DELEIDI M, et al. Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats[J]. Proc Natl Acad Sci USA, 2010, 107(36): 15921-15926.
[44]
NIU W, ZANG T, WANG L L, et al. Phenotypic reprogramming of striatal neurons into dopaminergic neuron-like cells in the adult mouse brain[J]. Stem Cell Reports, 2018, 11(5): 1156-1170.
[45]
KIKUCHI T, MORIZANE A, DOI D, et al. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson′s disease model[J]. Nature, 2017, 548(7669): 592-596.
[46]
YASUHARA T, KAMEDA M, SASAKI T, et al. Cell therapy for Parkinson′s disease[J]. Cell Transplant, 2017, 26(9): 1551-1559.
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