Fas Associated Factor 1 and Parkinson’s disease

• Type of Material: Article
• Authors: Ranjita Betarbet, Emory University; Tiffany R. Hodges, Duke University; Leah Anderson Roesch, Emory University; Marla Gearing, Emory University; Jason Jon Fritz, Emory University; James J Lah, Emory University; Allan I Levey, Emory University
• Language: English
• Date: 2008-09
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2008 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.nbd.2008.05.006
• Title of Journal or Parent Work: Neurobiology of Disease
• ISSN: 0969-9961
• Volume: 31
• Issue: 3
• Start Page: 309
• End Page: 315
• Grant/Funding Information: This work was supported by Close to A Cure funding agency (RB) and NIEHS grants ES012068 (AIL) & ES015777 (RB).
• Keywords: PARK 10; oxidative stress; α-synuclein; mitochondrial inhibition; cell death
• Research Categories: Health Sciences, Pathology; Biology, Neuroscience

Abstract

Fas-associated factor 1 or FAF1 is a Fas binding protein implicated in apoptosis. FAF1 is the product of a gene at PARK 10 locus on chromosome 1p32, a locus associated with late-onset PD (Hicks et al., 2002). In the present study we investigated the role of FAF1 in cell death and in Parkinson’s disease (PD) pathogenesis. FAF1 levels were significantly increased in frontal cortex of PD as well as in PD cases with Alzheimer’s disease (AD) pathology compared to control cases. Changes in FAF1 expression were specific to PD-related α-synuclein pathology and nigral cell loss. In addition, PD-related insults including, mitochondrial complex I inhibition, oxidative stress, and increased α-synuclein expression specifically increased endogenous FAF1 expression in vitro. Increased FAF1 levels induced cell death and significantly potentiated toxic effects of PD-related stressors including, oxidative stress, mitochondrial complex I inhibition and proteasomal inhibition. These studies, together with previous genetic linkage studies, highlight the potential significance of FAF1 in pathogenesis of idiopathic PD.