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:	Samar K. Alselehdar, Monami Chakraborty, Suman Chowdhury, Roy N. Alcalay, Matthew Surface, Robert Ledeen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	early diagnosis sporadic Parkinson’s disease GBA variant of Parkinson’s GM1 ganglioside GD1a ganglioside PBMCs Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/a0606aed9acc4f3cac756aa733a7c410
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spelling	oai:doaj.org-article:a0606aed9acc4f3cac756aa733a7c4102021-11-11T16:58:57ZSubnormal GM1 in PBMCs: Promise for Early Diagnosis of Parkinson’s Disease?10.3390/ijms2221115221422-00671661-6596https://doaj.org/article/a0606aed9acc4f3cac756aa733a7c4102021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11522https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The 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.Samar K. AlselehdarMonami ChakrabortySuman ChowdhuryRoy N. AlcalayMatthew SurfaceRobert LedeenMDPI AGarticleearly diagnosissporadic Parkinson’s diseaseGBA variant of Parkinson’sGM1 gangliosideGD1a gangliosidePBMCsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11522, p 11522 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	early diagnosis sporadic Parkinson’s disease GBA variant of Parkinson’s GM1 ganglioside GD1a ganglioside PBMCs Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	early diagnosis sporadic Parkinson’s disease GBA variant of Parkinson’s GM1 ganglioside GD1a ganglioside PBMCs Biology (General) QH301-705.5 Chemistry QD1-999 Samar K. Alselehdar Monami Chakraborty Suman Chowdhury Roy N. Alcalay Matthew Surface Robert Ledeen Subnormal GM1 in PBMCs: Promise for Early Diagnosis of Parkinson’s Disease?
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.
format	article
author	Samar K. Alselehdar Monami Chakraborty Suman Chowdhury Roy N. Alcalay Matthew Surface Robert Ledeen
author_facet	Samar K. Alselehdar Monami Chakraborty Suman Chowdhury Roy N. Alcalay Matthew Surface Robert Ledeen
author_sort	Samar K. Alselehdar
title	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_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_sort	subnormal gm1 in pbmcs: promise for early diagnosis of parkinson’s disease?
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a0606aed9acc4f3cac756aa733a7c410
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Subnormal GM1 in PBMCs: Promise for Early Diagnosis of Parkinson’s Disease?

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