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

Alpha-MSH: Could this anti-inflammatory mediator be the culprit in Parkinson’s Disease?

Jay S. Dela Cruz
doi: https://doi.org/10.1101/2020.09.27.313957
Jay S. Dela Cruz
InTouch BioSolutions LLC, Moreno Valley, CA 92557 USA; E-mail: ; Phone: (951) 330-5482
Ph.D.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: jdelacruz@intouchbio.com jdelacruz@intouchbio.com
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Data/Code
  • Preview PDF
Loading

Abstract

We now show that key processes implicated in synuclein pathogenesis such as impairment of cellular autophagy and alpha-synuclein (α-syn) aggregation are induced by alpha-melanocyte stimulating hormone (alpha-MSH), a microglia-secreted anti-inflammatory mediator. We employed the pigmented melanoma cell line MNT-1 as a novel in-vitro cell model of melanin-containing dopaminergic neurons (DNs) of the substantia nigra (SN). Melanin levels serve as a reliable readout of autophagy in MNT-1 and exposure to alpha-MSH resulted in a decrease in melanin and a failure to slow down glucose consumption, which induced cell death by apoptosis. ASIP (agouti-signaling protein), the natural biologic inhibitor of alpha-MSH, blocked and reversed the effects of alpha-MSH. Mice administered intranasal alpha-MSH exhibited progressive decline in gait, a prevalent condition seen in patients with Parkinson’s Disease (PD). Moreover, we observed what may be α-syn aggregation in the SN pars compacta (SNpc). SNpc and striatal tyrosine hydroxylase (TH) density showed very modest reduction in this animal PD model consistent with PD pathology at the very early stage of disease.

Fundamental Questions Addressed by this Study

  1. What may be the pathophysiologic link between neuroinflammation and impairment of autophagy in PD?

  2. What may be a microglia-derived mediator that impairs autophagy and induces alpha-synuclein aggregation in dopaminergic neurons in PD?

  3. What drives neurotoxicity that could lead to oxidative stress and ROS-mediated cell loss in PD?

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://drive.google.com/file/d/1eIZgq1HSKPaRFLdbgCM-vuON_Qu14ukN/view?usp=sharing

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted September 29, 2020.
Download PDF
Data/Code
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.
Alpha-MSH: Could this anti-inflammatory mediator be the culprit in Parkinson’s Disease?
(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
Alpha-MSH: Could this anti-inflammatory mediator be the culprit in Parkinson’s Disease?
Jay S. Dela Cruz
bioRxiv 2020.09.27.313957; doi: https://doi.org/10.1101/2020.09.27.313957
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Alpha-MSH: Could this anti-inflammatory mediator be the culprit in Parkinson’s Disease?
Jay S. Dela Cruz
bioRxiv 2020.09.27.313957; doi: https://doi.org/10.1101/2020.09.27.313957

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 (4655)
  • Biochemistry (10307)
  • Bioengineering (7618)
  • Bioinformatics (26203)
  • Biophysics (13453)
  • Cancer Biology (10625)
  • Cell Biology (15348)
  • Clinical Trials (138)
  • Developmental Biology (8456)
  • Ecology (12761)
  • Epidemiology (2067)
  • Evolutionary Biology (16777)
  • Genetics (11361)
  • Genomics (15407)
  • Immunology (10556)
  • Microbiology (25060)
  • Molecular Biology (10162)
  • Neuroscience (54128)
  • Paleontology (398)
  • Pathology (1655)
  • Pharmacology and Toxicology (2877)
  • Physiology (4315)
  • Plant Biology (9204)
  • Scientific Communication and Education (1582)
  • Synthetic Biology (2543)
  • Systems Biology (6753)
  • Zoology (1453)