Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1784597312724533248 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8583888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT alselehdarsamark subnormalgm1inpbmcspromiseforearlydiagnosisofparkinsonsdisease AT chakrabortymonami subnormalgm1inpbmcspromiseforearlydiagnosisofparkinsonsdisease AT chowdhurysuman subnormalgm1inpbmcspromiseforearlydiagnosisofparkinsonsdisease AT alcalayroyn subnormalgm1inpbmcspromiseforearlydiagnosisofparkinsonsdisease AT surfacematthew subnormalgm1inpbmcspromiseforearlydiagnosisofparkinsonsdisease AT ledeenrobert subnormalgm1inpbmcspromiseforearlydiagnosisofparkinsonsdisease |