Cellular and Molecular Life Sciences

, Volume 72, Issue 4, pp 773–797 | Cite as

Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression

  • Jaclyn Nicole Le Grand
  • Laura Gonzalez-Cano
  • Maria Angeliki Pavlou
  • Jens C. 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.


Parkinson’s disease Neural stem cells Neurogenesis Development LRRK2 SNCA 





Atypical protein kinase C




Dentate gyrus


Double knockout


Drosophila neuroblasts


Embryonic stem cell


Induced pluripotent stem cell






Leucine-rich repeat kinase 2






Nuclear factor-kappaB


Neural progenitor cell


Neural stem cell


Olfactory bulb


Proliferating cell nuclear antigen


Parkinson’s disease


PTEN-induced putative kinase 1


Rostral migratory stream


Substantia nigra


Substantia nigra pars compacta




Subgranular zone


Subventricular zone


Tyrosine hydroxylase


Vacuolar protein sorting 35


Wild type



This work was supported by the Fonds National de la Recherche Luxembourg (FNR). Jaclyn Nicole Le Grand and Laura Gonzalez-Cano are supported by fellowships from the FNR (AFR, Aides à la Formation-Recherche).


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Copyright information

© Springer Basel 2014

Authors and Affiliations

  • Jaclyn Nicole Le Grand
    • 1
  • Laura Gonzalez-Cano
    • 1
  • Maria Angeliki Pavlou
    • 1
  • Jens C. Schwamborn
    • 1
  1. 1.Luxembourg Centre for Systems Biomedicine (LCSB)University of LuxembourgEsch-sur-AlzetteLuxembourg

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