Browse by author
Lookup NU author(s): Professor Heather Cordell
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
© 2016 Springer Science+Business Media New YorkThe cytoskeleton not only provides structure, it is an active component of cell function, and in several neurodegenerative disorders, there is evidence of cytoskeletal collapse. Cytoskeletal proteins have been specifically implicated in the pathogenesis of Parkinson’s disease (PD), where degeneration of dopaminergic (DA) neurons is the hallmark, but in which many factors may determine the resilience of DA neurons during aging and stress. Here we report that the human Microtubule Actin Cross-linking Factor 1 gene (MACF1), a downstream target of PD biochemical pathways, was significantly associated with PD in 713 nuclear families. A significant allelic association between PD and rs12118033, with P = 0.0098, was observed, and a P < 0.03 was observed in the association analysis by both a trend test and an allelic test. We further observed that it is the MACF1b isoform, not the MACF1a isoform, which is expressed in DA neurons from six human postmortem brains. In a Caenorhabditis elegans system, used to explore the effect of altered MACF1b on neurons, knockdown or knockout of the MACF1b orthologue vab-10 resulted in the selective loss of DA neurons, which validated MACF1’s risk candidacy in PD. These findings strongly suggest that MACF1b may contribute to the genetic etiology and mechanistic causation of PD.
Author(s): Wang X, Li N, Xiong N, You Q, Li J, Yu J, Qing H, Wang T, Cordell HJ, Isacson O, Vance JM, Martin ER, Zhao Y, Cohen BM, Buttner EA, Lin Z
Publication type: Article
Publication status: Published
Journal: Molecular Neurobiology
Year: 2016
Volume: 54
Issue: 4
Pages: 2878-2888
Print publication date: 01/05/2017
Online publication date: 28/03/2016
Acceptance date: 17/03/2016
ISSN (print): 0893-7648
ISSN (electronic): 1559-1182
Publisher: Humana Press Inc.
URL: http://doi.org/10.1007/s12035-016-9861-y
DOI: 10.1007/s12035-016-9861-y
Altmetrics provided by Altmetric
