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Subnormal GM1 in PBMCs: Promise for Early Diagnosis of Parkinson’s Disease?

The fact that Parkinson’s disease (PD) pathologies are well advanced in most PD patients by the time of clinical elucidation attests to the importance of early diagnosis. Our attempt to achieve this has capitalized on our previous finding that GM1 ganglioside is expressed at subnormal levels in virt...

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Autores principales: Alselehdar, Samar K., Chakraborty, Monami, Chowdhury, Suman, Alcalay, Roy N., Surface, Matthew, Ledeen, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583888/
https://www.ncbi.nlm.nih.gov/pubmed/34768952
http://dx.doi.org/10.3390/ijms222111522
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author Alselehdar, Samar K.
Chakraborty, Monami
Chowdhury, Suman
Alcalay, Roy N.
Surface, Matthew
Ledeen, Robert
author_facet Alselehdar, Samar K.
Chakraborty, Monami
Chowdhury, Suman
Alcalay, Roy N.
Surface, Matthew
Ledeen, Robert
author_sort Alselehdar, Samar K.
collection PubMed
description The fact that Parkinson’s disease (PD) pathologies are well advanced in most PD patients by the time of clinical elucidation attests to the importance of early diagnosis. Our attempt to achieve this has capitalized on our previous finding that GM1 ganglioside is expressed at subnormal levels in virtually all tissues of sporadic PD (sPD) patients including blood cells. GM1 is present in most vertebrate cells, is especially abundant in neurons where it was shown essential for their effective functioning and long term viability. We have utilized peripheral blood mononuclear cells (PBMCs) which, despite their low GM1, we found to be significantly lower in sPD patients compared to age-matched healthy controls. To quantify GM1 (and GD1a) we used high performance thin-layer chromatography combined with cholera toxin B linked to horseradish peroxidase, followed by densitometric quantification. GM1 was also deficient in PBMCs from PD patients with mutations in the glucocerebrosidase gene (PD-GBA), apparently even lower than in sPD. Reasons are given why we believe these results obtained with patients manifesting fully developed PD will apply as well to PD patients in preclinical stages—a topic for future study. We also suggest that these findings point to a potential disease altering therapy for PD once the early diagnosis is established.
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spelling pubmed-85838882021-11-12 Subnormal GM1 in PBMCs: Promise for Early Diagnosis of Parkinson’s Disease? Alselehdar, Samar K. Chakraborty, Monami Chowdhury, Suman Alcalay, Roy N. Surface, Matthew Ledeen, Robert Int J Mol Sci Article The fact that Parkinson’s disease (PD) pathologies are well advanced in most PD patients by the time of clinical elucidation attests to the importance of early diagnosis. Our attempt to achieve this has capitalized on our previous finding that GM1 ganglioside is expressed at subnormal levels in virtually all tissues of sporadic PD (sPD) patients including blood cells. GM1 is present in most vertebrate cells, is especially abundant in neurons where it was shown essential for their effective functioning and long term viability. We have utilized peripheral blood mononuclear cells (PBMCs) which, despite their low GM1, we found to be significantly lower in sPD patients compared to age-matched healthy controls. To quantify GM1 (and GD1a) we used high performance thin-layer chromatography combined with cholera toxin B linked to horseradish peroxidase, followed by densitometric quantification. GM1 was also deficient in PBMCs from PD patients with mutations in the glucocerebrosidase gene (PD-GBA), apparently even lower than in sPD. Reasons are given why we believe these results obtained with patients manifesting fully developed PD will apply as well to PD patients in preclinical stages—a topic for future study. We also suggest that these findings point to a potential disease altering therapy for PD once the early diagnosis is established. MDPI 2021-10-26 /pmc/articles/PMC8583888/ /pubmed/34768952 http://dx.doi.org/10.3390/ijms222111522 Text en © 2021 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 Article
Alselehdar, Samar K.
Chakraborty, Monami
Chowdhury, Suman
Alcalay, Roy N.
Surface, Matthew
Ledeen, Robert
Subnormal GM1 in PBMCs: Promise for Early Diagnosis of Parkinson’s Disease?
title Subnormal GM1 in PBMCs: Promise for Early Diagnosis of Parkinson’s Disease?
title_full Subnormal GM1 in PBMCs: Promise for Early Diagnosis of Parkinson’s Disease?
title_fullStr Subnormal GM1 in PBMCs: Promise for Early Diagnosis of Parkinson’s Disease?
title_full_unstemmed Subnormal GM1 in PBMCs: Promise for Early Diagnosis of Parkinson’s Disease?
title_short Subnormal GM1 in PBMCs: Promise for Early Diagnosis of Parkinson’s Disease?
title_sort subnormal gm1 in pbmcs: promise for early diagnosis of parkinson’s disease?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583888/
https://www.ncbi.nlm.nih.gov/pubmed/34768952
http://dx.doi.org/10.3390/ijms222111522
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