alpha-Synuclein Induces Alterations in Adult Neurogenesis in Parkinson Disease Models via p53-mediated Repression of Notch1
Winner B, Spencer B, Kosberg K, Roberts S, Patrick C, Winkler J, Masliah E (2012)
Publication Status: Published
Publication Type: Journal article
Publication year: 2012
Journal
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Book Volume: 287
Pages Range: 31691-31702
Journal Issue: 38
Abstract
Parkinson disease is characterized by the loss of dopaminergic neurons mainly in the substantia nigra. Accumulation of alpha-synuclein and cell loss has been also reported in many other brain regions including the hippocampus, where it might impair adult neurogenesis, contributing to nonmotor symptoms. However, the molecular mechanisms of these alterations are still unknown. In this report we show that alpha-synuclein-accumulating adult rat hippocampus neural progenitors present aberrant neuronal differentiation, with reduction of Notch1 expression and downstream signaling targets. We characterized a Notch1 proximal promoter that contains p53 canonical response elements. In vivo binding of p53 represses the transcription of Notch1 in neurons. Moreover, we demonstrated that alpha-synuclein directly binds to the DNA at Notch1 promoter vicinity and also interacts with p53 protein, facilitating or increasing Notch1 signaling repression, which interferes with maturation and survival of neural progenitors cells. This study provides a molecular basis for alpha-synuclein-mediated disruption of adult neurogenesis in Parkinson disease.
Authors with CRIS profile
Involved external institutions
University of California, San Diego
United States (USA) (US)
Mississippi State University for Agriculture and Applied Science
United States (USA) (US)
United States (USA) (US)
Mississippi State University for Agriculture and Applied Science
United States (USA) (US)
How to cite
APA:
Winner, B., Spencer, B., Kosberg, K., Roberts, S., Patrick, C., Winkler, J., & Masliah, E. (2012). alpha-Synuclein Induces Alterations in Adult Neurogenesis in Parkinson Disease Models via p53-mediated Repression of Notch1. Journal of Biological Chemistry, 287(38), 31691-31702. https://doi.org/10.1074/jbc.M112.354522
MLA:
Winner, Beate, et al. "alpha-Synuclein Induces Alterations in Adult Neurogenesis in Parkinson Disease Models via p53-mediated Repression of Notch1." Journal of Biological Chemistry 287.38 (2012): 31691-31702.
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