Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Novel insights in the pathophysiology of α-synuclein dysregulation on D2 receptor activity contributing to the vulnerability of dopamine neurons

Abeer Dagra, View ORCID ProfileDouglas R. Miller, Fatemeh Shaerzadeh, Min Lin, Adithya Gopinath, Sharonda Harris, Zachary A. Sorrentino, Sophia Velasco, Adetola R Alonge, Janelle Azar, Joe J Lebowitz, Brittany Ulm, Anthea-Mengfei Bu, Carissa A. Hansen, View ORCID ProfileNikhil Urs, Benoit I. Giasson, Habibeh Khoshbouei
doi: https://doi.org/10.1101/2021.03.30.437775
Abeer Dagra
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Douglas R. Miller
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Douglas R. Miller
Fatemeh Shaerzadeh
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Min Lin
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adithya Gopinath
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sharonda Harris
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zachary A. Sorrentino
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sophia Velasco
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adetola R Alonge
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Janelle Azar
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joe J Lebowitz
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brittany Ulm
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anthea-Mengfei Bu
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carissa A. Hansen
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nikhil Urs
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Nikhil Urs
Benoit I. Giasson
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: habibeh@ufl.edu bgiasson@ufl.edu
Habibeh Khoshbouei
1Department of Neuroscience, University of Florida; Gainesville, Florida, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: habibeh@ufl.edu bgiasson@ufl.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Pathophysiological damages and loss of function of dopamine neurons precedes their demise and contributes to the early phases of Parkinson’s disease. The presence of aberrant intercellular pathological inclusions of the protein α-synuclein within ventral midbrain dopaminergic neurons is one of the cardinal features of Parkinson’s disease. We employed multiple complementary approaches in molecular biology, electrophysiology, and live-cell imaging to investigate how excessive α-synuclein levels alters multiple characteristics of dopaminergic neuronal dynamics and dopamine transmission prior to neuronal demise. These studies demonstrate that α-synuclein dysregulation of D2 receptor autoinhibition contributes to the vulnerability of dopaminergic neurons, and that modulation thereof can ameliorate the resulting pathophysiology. These novel findings provide mechanistic insights in the insidious loss of dopaminergic function and neurons that characterize Parkinson’s disease progression with significant therapeutic implications.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted March 30, 2021.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Novel insights in the pathophysiology of α-synuclein dysregulation on D2 receptor activity contributing to the vulnerability of dopamine neurons
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Novel insights in the pathophysiology of α-synuclein dysregulation on D2 receptor activity contributing to the vulnerability of dopamine neurons
Abeer Dagra, Douglas R. Miller, Fatemeh Shaerzadeh, Min Lin, Adithya Gopinath, Sharonda Harris, Zachary A. Sorrentino, Sophia Velasco, Adetola R Alonge, Janelle Azar, Joe J Lebowitz, Brittany Ulm, Anthea-Mengfei Bu, Carissa A. Hansen, Nikhil Urs, Benoit I. Giasson, Habibeh Khoshbouei
bioRxiv 2021.03.30.437775; doi: https://doi.org/10.1101/2021.03.30.437775
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Novel insights in the pathophysiology of α-synuclein dysregulation on D2 receptor activity contributing to the vulnerability of dopamine neurons
Abeer Dagra, Douglas R. Miller, Fatemeh Shaerzadeh, Min Lin, Adithya Gopinath, Sharonda Harris, Zachary A. Sorrentino, Sophia Velasco, Adetola R Alonge, Janelle Azar, Joe J Lebowitz, Brittany Ulm, Anthea-Mengfei Bu, Carissa A. Hansen, Nikhil Urs, Benoit I. Giasson, Habibeh Khoshbouei
bioRxiv 2021.03.30.437775; doi: https://doi.org/10.1101/2021.03.30.437775

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (3482)
  • Biochemistry (7329)
  • Bioengineering (5301)
  • Bioinformatics (20212)
  • Biophysics (9985)
  • Cancer Biology (7706)
  • Cell Biology (11273)
  • Clinical Trials (138)
  • Developmental Biology (6425)
  • Ecology (9923)
  • Epidemiology (2065)
  • Evolutionary Biology (13292)
  • Genetics (9353)
  • Genomics (12559)
  • Immunology (7681)
  • Microbiology (18964)
  • Molecular Biology (7421)
  • Neuroscience (40915)
  • Paleontology (298)
  • Pathology (1226)
  • Pharmacology and Toxicology (2130)
  • Physiology (3145)
  • Plant Biology (6842)
  • Scientific Communication and Education (1271)
  • Synthetic Biology (1893)
  • Systems Biology (5299)
  • Zoology (1086)