NDLI: A Systematic RNAi Screen of Neuroprotective Genes Identifies Novel Modulators of Alpha-Synuclein-Associated Effects in Transgenic Caenorhabditis elegans

Content Provider	Springer Nature Link
Author	Jadiya, Pooja Fatima, Soobiya Baghel, Tanvi Mir, Sber S. Nazir, Aamir
Copyright Year	2015
Abstract	Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder, defined clinically by degeneration of dopaminergic neurons and the development of neuronal Lewy bodies. Current treatments of PD are inadequate due to a limited understanding of molecular events of the disease, thus calling for intense research efforts towards identification of novel therapeutic targets. We carried out the present studies towards identifying novel genetic modulators of PD-associated effects employing a transgenic Caenorhabditis elegans model expressing human alpha-synuclein. Employing a systematic RNA interference (RNAi)-based screening approach, we studied a set of neuroprotective genes of C. elegans with an aim of identifying genes that exhibit protective function under alpha-synuclein expression conditions. Our results reveal a novel set of alpha-synuclein effector genes that modulate alpha-synuclein aggregation and associated effects. The identified genes include those from various gene families including histone demethylase, lactate dehydrogenase, small ribosomal subunit SA protein, cytoskeletal protein, collapsin response mediator protein, and choline kinase. The functional characterization of these genes reveals involvement of signaling mechanisms such as Daf-16 and acetylcholine signaling. Further elucidation of mechanistic pathways associated with these genes will yield additional insights into mediators of alpha-synuclein-induced cytotoxicity and cell death, thereby helping in the identification of potential therapeutic targets for PD.
Starting Page	6288
Ending Page	6300
Page Count	13
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	53
Issue Number	9
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2015-11-14
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Parkinson’s disease Alpha-synuclein Neuroprotective genes Caenorhabditis elegans Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

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