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The Key Role of GM1 Ganglioside in Parkinson’s Disease

We have endeavored in this review to summarize our findings, which point to a systemic deficiency of ganglioside GM1 in Parkinson’s disease (PD) tissues. These include neuronal tissues well known to be involved in PD, such as substantia nigra of the brain and those of the peripheral nervous system,...

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Detalles Bibliográficos
Autores principales: Chowdhury, Suman, Ledeen, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961665/
https://www.ncbi.nlm.nih.gov/pubmed/35204675
http://dx.doi.org/10.3390/biom12020173
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author Chowdhury, Suman
Ledeen, Robert
author_facet Chowdhury, Suman
Ledeen, Robert
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description We have endeavored in this review to summarize our findings, which point to a systemic deficiency of ganglioside GM1 in Parkinson’s disease (PD) tissues. These include neuronal tissues well known to be involved in PD, such as substantia nigra of the brain and those of the peripheral nervous system, such as the colon and heart. Moreover, we included skin and fibroblasts in the study as well as peripheral blood mononuclear cells; these are tissues not directly involved in neuronal signaling. We show similar findings for ganglioside GD1a, which is the metabolic precursor to GM1. We discuss the likely causes of these GM1 deficiencies and the resultant biochemical mechanisms underlying loss of neuronal viability and normal functioning. Strong support for this hypothesis is provided by a mouse PD model involving partial GM1 deficiency based on mono-allelic disruption of the B4galnt1 gene. We point out that progressive loss of GM1/GD1a occurs in the periphery as well as the brain, thus obviating the need to speculate PD symptom transfer between these tissues. Finally, we discuss how these findings point to a potential disease-altering therapy for PD:GM1 replacement, as is strongly implicated in animal studies and clinical trials.
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spelling pubmed-89616652022-03-30 The Key Role of GM1 Ganglioside in Parkinson’s Disease Chowdhury, Suman Ledeen, Robert Biomolecules Review We have endeavored in this review to summarize our findings, which point to a systemic deficiency of ganglioside GM1 in Parkinson’s disease (PD) tissues. These include neuronal tissues well known to be involved in PD, such as substantia nigra of the brain and those of the peripheral nervous system, such as the colon and heart. Moreover, we included skin and fibroblasts in the study as well as peripheral blood mononuclear cells; these are tissues not directly involved in neuronal signaling. We show similar findings for ganglioside GD1a, which is the metabolic precursor to GM1. We discuss the likely causes of these GM1 deficiencies and the resultant biochemical mechanisms underlying loss of neuronal viability and normal functioning. Strong support for this hypothesis is provided by a mouse PD model involving partial GM1 deficiency based on mono-allelic disruption of the B4galnt1 gene. We point out that progressive loss of GM1/GD1a occurs in the periphery as well as the brain, thus obviating the need to speculate PD symptom transfer between these tissues. Finally, we discuss how these findings point to a potential disease-altering therapy for PD:GM1 replacement, as is strongly implicated in animal studies and clinical trials. MDPI 2022-01-21 /pmc/articles/PMC8961665/ /pubmed/35204675 http://dx.doi.org/10.3390/biom12020173 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Chowdhury, Suman
Ledeen, Robert
The Key Role of GM1 Ganglioside in Parkinson’s Disease
title The Key Role of GM1 Ganglioside in Parkinson’s Disease
title_full The Key Role of GM1 Ganglioside in Parkinson’s Disease
title_fullStr The Key Role of GM1 Ganglioside in Parkinson’s Disease
title_full_unstemmed The Key Role of GM1 Ganglioside in Parkinson’s Disease
title_short The Key Role of GM1 Ganglioside in Parkinson’s Disease
title_sort key role of gm1 ganglioside in parkinson’s disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961665/
https://www.ncbi.nlm.nih.gov/pubmed/35204675
http://dx.doi.org/10.3390/biom12020173
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