caa a22 4500 606176543 CHVBK 20210128100748.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s00018-014-1774-1 doi (NATIONALLICENCE)springer-10.1007/s00018-014-1774-1 Neural stem cells in Parkinson's disease: a role for neurogenesis defects in onset and progression [Elektronische Daten] [Jaclyn Le Grand, Laura Gonzalez-Cano, Maria Pavlou, Jens Schwamborn] Parkinson's disease (PD) is the second most common neurodegenerative disorder, leading to a variety of motor and non-motor symptoms. Interestingly, non-motor symptoms often appear a decade or more before the first signs of motor symptoms. Some of these non-motor symptoms are remarkably similar to those observed in cases of impaired neurogenesis and several PD-related genes have been shown to play a role in embryonic or adult neurogenesis. Indeed, animal models deficient in Nurr1, Pitx3, SNCA and PINK1 display deregulated embryonic neurogenesis and LRRK2 and VPS35 have been implicated in neuronal development-related processes such as Wnt/β-catenin signaling and neurite outgrowth. Moreover, adult neurogenesis is affected in both PD patients and PD animal models and is regulated by dopamine and dopaminergic (DA) receptors, by chronic neuroinflammation, such as that observed in PD, and by differential expression of wild-type or mutant forms of PD-related genes. Indeed, an increasing number of in vivo studies demonstrate a role for SNCA and LRRK2 in adult neurogenesis and in the generation and maintenance of DA neurons. Finally, the roles of PD-related genes, SNCA, LRRK2, VPS35, Parkin, PINK1 and DJ-1 have been studied in NSCs, progenitor cells and induced pluripotent stem cells, demonstrating a role for some of these genes in stem/progenitor cell proliferation and maintenance. Together, these studies strongly suggest a link between deregulated neurogenesis and the onset and progression of PD and present strong evidence that, in addition to a neurodegenerative disorder, PD can also be regarded as a developmental disorder. Springer Basel, 2014 Parkinson's disease nationallicence Neural stem cells nationallicence Neurogenesis nationallicence Development nationallicence LRRK2 nationallicence SNCA nationallicence 6-OHDA : 6-Hydroxydopamine nationallicence aPKC : Atypical protein kinase C nationallicence DA : Dopaminergic nationallicence DG : Dentate gyrus nationallicence DKO : Double knockout nationallicence dNB : Drosophila neuroblasts nationallicence ESC : Embryonic stem cell nationallicence iPSC : Induced pluripotent stem cell nationallicence KD : Knockdown nationallicence KO : Knockout nationallicence LRRK2 : Leucine-rich repeat kinase 2 nationallicence MPTP : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine nationallicence NB : Neuroblast nationallicence NF-κB : Nuclear factor-kappaB nationallicence NPC : Neural progenitor cell nationallicence NSC : Neural stem cell nationallicence OB : Olfactory bulb nationallicence PCNA : Proliferating cell nuclear antigen nationallicence PD : Parkinson's disease nationallicence PINK1 : PTEN-induced putative kinase 1 nationallicence RMS : Rostral migratory stream nationallicence SN : Substantia nigra nationallicence SNpc : Substantia nigra pars compacta nationallicence SNCA : α-Synuclein nationallicence SGZ : Subgranular zone nationallicence SVZ : Subventricular zone nationallicence TH : Tyrosine hydroxylase nationallicence VPS35 : Vacuolar protein sorting 35 nationallicence WT : Wild type nationallicence Le Grand Jaclyn Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362, Esch-sur-Alzette, Luxembourg aut Gonzalez-Cano Laura Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362, Esch-sur-Alzette, Luxembourg aut Pavlou Maria Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362, Esch-sur-Alzette, Luxembourg aut Schwamborn Jens Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362, Esch-sur-Alzette, Luxembourg aut Cellular and Molecular Life Sciences Springer Basel 72/4(2015-02-01), 773-797 1420-682X 72:4<773 2015 72 18 https://doi.org/10.1007/s00018-014-1774-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-014-1774-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Le Grand Jaclyn Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362, Esch-sur-Alzette, Luxembourg aut NATIONALLICENCE 700 1- Gonzalez-Cano Laura Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362, Esch-sur-Alzette, Luxembourg aut NATIONALLICENCE 700 1- Pavlou Maria Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362, Esch-sur-Alzette, Luxembourg aut NATIONALLICENCE 700 1- Schwamborn Jens Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 4362, Esch-sur-Alzette, Luxembourg aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/4(2015-02-01), 773-797 1420-682X 72:4<773 2015 72 18