Publications by authors named "Aurelia Hays Watson"
Article Synopsis
- Researchers focused on how different forms of α-synuclein (monomers and multimers) affect synaptic processes using lamprey synapses for their experiments.
- Both forms impaired vesicle trafficking, but they had distinct effects: monomers caused abnormal fusion/fission and disrupted endocytosis, while multimers decreased vesicle docking.
Article Synopsis
- - The study focuses on synucleinopathies, specifically Parkinson's disease (PD), characterized by the buildup of α-synuclein protein in the brain and other tissues.
- - Researchers examined blood samples from familial PD patients with G51D mutations and sporadic PD patients, finding that levels of stable α-synuclein tetramers were lower compared to control groups.
- - The decrease in α-synuclein tetramers was also observed in asymptomatic G51D carriers, suggesting that destabilization of these proteins may occur before the onset of PD symptoms, pointing to their potential use as early biomarkers for the disease.
In Parkinson's disease and other synucleinopathies, the elevation of α-synuclein phosphorylated at Serine129 (pS129) is a widely cited marker of pathology. However, the physiological role for pS129 has remained undefined. Here we use multiple approaches to show for the first time that pS129 functions as a physiological regulator of neuronal activity.
View Article and Find Full Text PDFThe protein α-synuclein, a key player in Parkinson's disease (PD) and other synucleinopathies, exists in different physiological conformations: cytosolic unfolded aggregation-prone monomers and helical aggregation-resistant multimers. It has been shown that familial PD-associated missense mutations within the α-synuclein gene destabilize the conformer equilibrium of physiologic α-synuclein in favor of unfolded monomers. Here, we characterized the relative levels of unfolded and helical forms of cytosolic α-synuclein in post-mortem human brain tissue and showed that the equilibrium of α-synuclein conformations is destabilized in sporadic PD and DLB patients.
View Article and Find Full Text PDFSince researchers identified α-synuclein as the principal component of Lewy bodies and Lewy neurites, studies have suggested that it plays a causative role in the pathogenesis of dementia with Lewy bodies and other 'synucleinopathies'. While α-synuclein dyshomeostasis likely contributes to the neurodegeneration associated with the synucleinopathies, few direct biochemical analyses of α-synuclein from diseased human brain tissue currently exist. In this study, we analysed sequential protein extracts from a substantial number of patients with neuropathological diagnoses of dementia with Lewy bodies and corresponding controls, detecting a shift of cytosolic and membrane-bound physiological α-synuclein to highly aggregated forms.
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