Subnormal GM1 in PBMCs: Promise for Early Diagnosis of Parkinson's Disease?
Autor: | Suman Chowdhury, Robert W. Ledeen, Roy N. Alcalay, Monami Chakraborty, Matthew Surface, Samar K. Alselehdar |
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Rok vydání: | 2021 |
Předmět: |
GBA variant of Parkinson’s
Male Parkinson's disease Disease medicine.disease_cause HPTLC GD1a ganglioside Gangliosides Biology (General) sporadic Parkinson’s disease Spectroscopy Cholera toxin Parkinson Disease General Medicine Middle Aged Computer Science Applications Gm1 ganglioside Fully developed Chemistry Glucosylceramidase Female QH301-705.5 G(M1) Ganglioside Peripheral blood mononuclear cell Article Catalysis Inorganic Chemistry medicine Humans Physical and Theoretical Chemistry cholera toxin B Molecular Biology QD1-999 Aged business.industry Organic Chemistry medicine.disease Future study Early Diagnosis ROC Curve Case-Control Studies Immunology PBMCs Mutation Leukocytes Mononuclear GM1 ganglioside business Glucocerebrosidase Biomarkers Blood Chemical Analysis |
Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 11522, p 11522 (2021) International Journal of Molecular Sciences Volume 22 Issue 21 |
ISSN: | 1422-0067 |
Popis: | 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. |
Databáze: | OpenAIRE |
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