Cellular and Molecular Life Sciences

, Volume 72, Issue 4, pp 773–797

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
Review

DOI: 10.1007/s00018-014-1774-1

Cite this article as:
Le Grand, J.N., Gonzalez-Cano, L., Pavlou, M.A. et al. Cell. Mol. Life Sci. (2015) 72: 773. doi:10.1007/s00018-014-1774-1

Abstract

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.

Keywords

Parkinson’s diseaseNeural stem cellsNeurogenesisDevelopmentLRRK2SNCA

Abbreviations

6-OHDA

6-Hydroxydopamine

aPKC

Atypical protein kinase C

DA

Dopaminergic

DG

Dentate gyrus

DKO

Double knockout

dNB

Drosophila neuroblasts

ESC

Embryonic stem cell

iPSC

Induced pluripotent stem cell

KD

Knockdown

KO

Knockout

LRRK2

Leucine-rich repeat kinase 2

MPTP

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NB

Neuroblast

NF-κB

Nuclear factor-kappaB

NPC

Neural progenitor cell

NSC

Neural stem cell

OB

Olfactory bulb

PCNA

Proliferating cell nuclear antigen

PD

Parkinson’s disease

PINK1

PTEN-induced putative kinase 1

RMS

Rostral migratory stream

SN

Substantia nigra

SNpc

Substantia nigra pars compacta

SNCA

α-Synuclein

SGZ

Subgranular zone

SVZ

Subventricular zone

TH

Tyrosine hydroxylase

VPS35

Vacuolar protein sorting 35

WT

Wild type

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