Questions, Feedback & Help
Send us an email and we'll get back to you ASAP. Or you can read our Frequently Asked Questions.
  • page settings
  • hide sidebar
  • show empty fields
  • layout
  • (too narrow)
  • open all
  • close all
Resources » Paper

Nass, Richard et al. (2015) International Worm Meeting "The identification and characterization of SKN-1-associated acetylation pathways involved in dopamine neurodegeneration in Parkinson's disease models."

  • History

  • Referenced

  • Tree Display

  • My Favorites

  • My Library

  • Comments on Nass, Richard et al. (2015) International Worm Meeting "The identification and characterization of SKN-1-associated acetylation pathways involved in dopamine neurodegeneration in Parkinson's disease models." (0)

  • Overview

    Status:
    Publication type:
    Meeting_abstract
    WormBase ID:
    WBPaper00048016

    Nass, Richard, Trinidad, Jonathan, Shi, Jing, & Ren, Karen (2015). The identification and characterization of SKN-1-associated acetylation pathways involved in dopamine neurodegeneration in Parkinson's disease models presented in International Worm Meeting. Unpublished information; cite only with author permission.

    Background: Idiopathic Parkinson's disease (PD) is an oxidative stress-related disorder that result in abnormal dopamine (DA) signaling and cell death. Although the origin of the pathogenesis in PD remains unclear, corollary evidence suggests both genetic and environmental contributions. The overlapping molecular determinants involved in the neuropathology in both genetic- and toxicant-associated PD models are largely ill defined. Aims: In this study we asked what are the common genes, molecular pathways and mechanisms involved in PD-associated DA neuron vulnerability. Methods: We utilized reverse genetics, biochemical assays, immunofluorescence, transgenic C. elegans, RT-PCR, Western analysis, LC/MS, and neuronal morphology analysis to characterize expression and localization of the PD-associated transcription factor SKN-1 and a gene involved in protein acetylation play in several genetic- and toxicant-associated C. elegans PD models. Results: In this study we demonstrate that a gene involved in protein acetylation renders the DA neurons up to 15-fold more resistant to PD-associated genetic mutations or neurotoxicants, and that overexpression results in a 2-fold increase in DA neurodegeneration. We have also generated a C. elegans mutant that results in highly dysfunctional protein acetylation and an age dependent complete loss of DA neurons in young adult nematodes. The generation of the first C. elegans acetylome as well as reverse genetics and biochemical assays indicates SKN-1 modulates the protein acetylation that effect PD-associated DA neuron vulnerability. Conclusions: This study identifies novel genes and molecular pathways involved in DA neuron vulnerability, and provides in vivo evidence that a common epigenetic mechanism likely plays a significant role in PD-associated neurodegeneration. Support: NIH, BRG, Alzheimer's Disease Foundation, and FNDR Fund to RN, IUCRG to RN and JT.

    Affiliations:
    - Pharmacology & Toxicology, Indiana Univ Sch Med, Indianapolis, IN
    - Chemistry, Indiana University, Bloomington, IN


    Tip: Seeing your name marked red? Please help us identify you.