Biochemical Profiling of the Brain and Blood Metabolome in a Mouse Model of Prodromal Parkinson's Disease Reveals Distinct Metabolic Profiles

Journal of Proteome Research
Stewart F GrahamPatrik Brundin

Abstract

Parkinson's disease is the second most common neurodegenerative disease. In the vast majority of cases the origin is not genetic and the cause is not well understood, although progressive accumulation of α-synuclein aggregates appears central to the pathogenesis. Currently, treatments that slow disease progression are lacking, and there are no robust biomarkers that can facilitate the development of such treatments or act as aids in early diagnosis. Therefore, we have defined metabolomic changes in the brain and serum in an animal model of prodromal Parkinson's disease. We biochemically profiled the brain tissue and serum in a mouse model with progressive synucleinopathy propagation in the brain triggered by unilateral injection of preformed α-synuclein fibrils in the olfactory bulb. In total, we accurately identified and quantified 71 metabolites in the brain and 182 in serum using 1H NMR and targeted mass spectrometry, respectively. Using multivariate analysis, we accurately identified which metabolites explain the most variation between cases and controls. Using pathway enrichment analysis, we highlight significantly perturbed biochemical pathways in the brain and correlate these with the progression of the disease. Furtherm...Continue Reading

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Citations

Jan 13, 2019·Molecular Neurodegeneration·Yaping Shao, Weidong Le
Jul 3, 2019·Communications Biology·Ilia KurochkinPhilipp Khaitovich
Jul 1, 2020·CNS Neuroscience & Therapeutics·Michael Ugrumov
Apr 26, 2020·Metabolomics : Official Journal of the Metabolomic Society·Stewart F GrahamRay O Bahado-Singh
Aug 23, 2020·International Journal of Molecular Sciences·Stephanie M Grant, Sharon DeMorrow
Jan 12, 2020·Communications Biology·Ilia KurochkinPhilipp Khaitovich
Feb 23, 2021·Frontiers in Neuroscience·Yanyan ZhangTian Tian
Jul 7, 2021·Expert Review of Proteomics·Nimisha GuptaSaima Wajid

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Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.

Alpha-Synuclein Aggregation

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.