title: A Systematic RNAi Screen of Neuroprotective Genes Identifies Novel Modulators of Alpha-Synuclein-Associated Effects in Transgenic Caenorhabditis elegans.
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.
authors.affiliation: Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi, 110 001, India.|Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, 226 031, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Jadiya
authors.affiliation: Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, 226 031, India.|Department of Bioengineering, Integral University, Kursi Road, Lucknow, 226 026, India.
authors.forename: Soobiya
authors.initials: S
authors.lastname: Fatima
authors.affiliation: Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, 226 031, India.
authors.forename: Tanvi
authors.initials: T
authors.lastname: Baghel
authors.affiliation: Department of Bioengineering, Integral University, Kursi Road, Lucknow, 226 026, India.
authors.forename: Snober S
authors.initials: SS
authors.lastname: Mir
authors.affiliation: Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi, 110 001, India. anazir@cdri.res.in.|Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, 226 031, India. anazir@cdri.res.in.
authors.forename: Aamir
authors.initials: A
authors.lastname: Nazir
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D017238:Genes, Helminth; D008055:Lipids / Q000032:analysis; D008124:Locomotion; D008928:Mitochondria / Q000378:metabolism; D000066829:Neuroprotection / Q000235:genetics*; D066329:Protein Aggregates; D021381:Protein Transport; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013194:Staining and Labeling; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D008055:Lipids; D066329:Protein Aggregates; D017382:Reactive Oxygen Species; D051844:alpha-Synuclein; D000109:Acetylcholine; D004298:Dopamine
keywords: Alpha-synuclein; Caenorhabditis elegans; Neuroprotective genes; Parkinson’s disease