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BIBTEX RIS

Emerging role of LRRK2 in human neural progenitor cell cycle progression, survival and differentiation

2009; BioMed Central; Volume: 4; Issue: 1 Linguagem: Inglês

10.1186/1750-1326-4-25

ISSN

1750-1326

Autores

Javorina Milošević, Sigrid C. Schwarz, Vera Ogunlade, Anne K. Meyer, Alexander Storch, Johannes Schwarz,

Tópico(s)

Genomics and Chromatin Dynamics

Resumo

Despite a comprehensive mapping of the Parkinson's disease (PD)-related mRNA and protein leucine-rich repeat kinase 2 (LRRK2) in the mammalian brain, its physiological function in healthy individuals remains enigmatic. Based on its structural features and kinase properties, LRRK2 may interact with other proteins involved in signalling pathways. Here, we show a widespread LRRK2 mRNA and/or protein expression in expanded or differentiated human mesencephalic neural progenitor cells (hmNPCs) and in post-mortem substantia nigra PD patients. Using small interfering RNA duplexes targeting LRRK2 in hmNPCs following their differentiation into glia and neurons, we observed a reduced number of dopaminergic neurons due to apoptosis in LRRK2 knockdown samples. LRRK2-deficient hmNPCs exhibited elevated cell cycle- and cell death-related markers. In conclusion, a reduction of LRRK2 expression in hmNPCs severely impaired dopaminergic differentiation and/or survival of dopaminergic neurons most likely via preserving or reactivating the cell cycle.

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