UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date

2020-10-26

Document Type

Poster

Disciplines

Biochemistry | Molecular and Cellular Neuroscience | Molecular Biology | Nervous System Diseases

Abstract

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease is the most common form of motor neuron disease. In familial ALS, Multiple mutations of, PFN1 gene a well-known actin-binding protein have been linked to ALS disease recently. Phosphorylation in many degenerative conditions plays an important role in disease mechanism but its potential role in ALS remains not fully understood. We sought to look further into not previously studied phosphorylation of PFN1 as a potential contributor to aggregation and toxicity in ALS. Using different histochemistry and cytochemistry and molecular biology approaches, we observed that phosphorylation on Profilin shows a very distinctive pattern in PFN1C71G andSOD1G93A disease models. This modification is abundantly found in both astrocytes and white matter which latter indeed marks a staining pattern that is indistinguishable between two ALS mice model compared to controls. Interestingly, pPFN1 reactive areas colocalized with Myelin in the spinal cord are frequently found in the proximity of CD68 positive macrophages. Moreover, biochemical fractionation using ultracentrifugation detects endogenous pPFN1 in the highly insoluble fraction of protein lysate from both PFN1C71G andSOD1G93A model. Finally, a similar staining pattern to the ALS mice model was also observed in human sporadic ALS cases. Overall, our results suggest for the first time a role for phosphorylation of PFN1 in protein aggregation and white matter pathology in ALS that will shed more light on the mechanism of disease and developing potential therapeutics in near future.

Keywords

ALS, PFN1, Protein aggregation, phosphorylation

Rights and Permissions

Copyright © 2020 The Author(s). This is an open access document distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI of Published Version

10.13028/40e0-pc88

Journal/Book/Conference Title

25th Annual University of Massachusetts Medical School Research Retreat 2020

Comments

Poster presented virtually at the 25th Annual University of Massachusetts Medical School Research Retreat 2020 on October 26, 2020.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Available for download on Tuesday, May 04, 2021

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