Pathological role of lipid interaction with α-synuclein in Parkinson's disease

Neurochemistry International
Mari SuzukiYoshitaka Nagai

Abstract

Alpha-synuclein (αSyn) plays a central role in the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In sporadic PD and DLB, normally harmless αSyn proteins without any mutations might gain toxic functions by unknown mechanisms. Thus, it is important to elucidate the factors promoting the toxic conversion of αSyn, towards understanding the pathogenesis of and developing disease-modifying therapies for PD and DLB. Accumulating biophysical and biochemical studies have demonstrated that αSyn interacts with lipid membrane, and the interaction influences αSyn oligomerization and aggregation. Furthermore, genetic and clinicopathological studies have revealed mutations in the glucocerebrosidase 1 (GBA1) gene, which encodes a degrading enzyme for the glycolipid glucosylceramide (GlcCer), as strong risk factors for PD and DLB, and we recently demonstrated that GlcCer promotes toxic conversion of αSyn. Moreover, pathological studies have shown the existence of αSyn pathology in lysosomal storage disorders (LSDs) patient' brain, in which glycosphingolipids (GSLs) is found to be accumulated. In this review, we focus on the lipids as a key factor for inducing wild-type (WT) αSyn toxic conversion, we summarize the...Continue Reading

Citations

Dec 28, 2018·Movement Disorders : Official Journal of the Movement Disorder Society·Fabio BlandiniJosé L Lanciego
Mar 4, 2020·Nutritional Neuroscience·Peng Li, Cai Song
Jul 12, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·Katharina Klatt-SchreinerIrmgard Tegeder
Jul 25, 2019·Frontiers in Neuroscience·Kensuke IkenakaYoshitaka Nagai
Jun 30, 2019·Disease Models & Mechanisms·Lucie ValekIrmgard Tegeder
Jul 18, 2020·International Journal of Molecular Sciences·Shani BlumenreichAnthony H Futerman
Jan 27, 2019·Lipids in Health and Disease·Ghulam HussainTao Sun
Nov 16, 2019·NPJ Parkinson's Disease·Bryan A KillingerJeffrey H Kordower
Mar 27, 2020·Frontiers in Cellular Neuroscience·Deqiang HanZhiguo Chen
Jul 6, 2019·Frontiers in Neuroscience·Jiangnan MaAnmu Xie
Nov 5, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Florian GeltingerMark Rinnerthaler
Jan 13, 2021·Metabolic Brain Disease·Mei-Xue DongLing Hu
Jan 16, 2021·Frontiers in Neuroendocrinology·Daniel Báez CastellanosJanneth González
May 12, 2021·Neuropathology and Applied Neurobiology·Lucie ValekIrmgard Tegeder
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Irina A GuschinaVladimir L Buchman
Apr 19, 2020·Biochimica Et Biophysica Acta. Biomembranes·Regina AdãoMargarida Bastos
Nov 7, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Matthew SurfaceRoy N Alcalay

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