LMB Seminar - Alpha-Synuclein and its aggregation: Past, Present and Future

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• Maria Grazia Spillantini, University of Cambridge, Dept of Clinical Neurosciences
• Monday 10 February 2025, 11:00-12:00
• In person in the Max Perutz Lecture Theatre (CB2 0QH) and via Zoom link https://mrc-lmb-cam-ac-uk.zoom.us/j/98728840077?pwd=Z0MZ2xWLsyUC6fI31cIklaUbSYALwy.1.

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Most neurodegenerative diseases are characterised by the presence of abnormal intracellular protein inclusions. These inclusions were described at the beginning of last century as the defining neuropathological features of diseases, such as Alzheimer’s, Pick’s and Parkinson’s. In Alzheimer’s, Pick’s and several other diseases, the inclusions are made of the microtubule-associated protein tau. The filamentous inclusions of Parkinson’s disease, in the form of Lewy bodies and Lewy neurites, are made of the protein alpha-synuclein; the same is true of the Lewy pathology of dementia with Lewy bodies and the glial cytoplasmic inclusions of multiple system atrophy. Alpha-synuclein aggregates can be also found in about 60% of Alzheimer’s cases. The importance of the assembly of alpha-synuclein in these diseases is supported by the finding that mutations in its gene (SNCA) cause disease and these disorders are now also known as alpha-synucleinopathies. Studies on the distribution of Lewy pathology have suggested that in Parkinson’s disease alpha-synuclein aggregation begins in the periphery and spreads to the brain, resulting in pre-motor and then motor symptoms. Besides the Lewy bodies in the substantia nigra and other brain areas, smaller alpha-synuclein aggregates are present at synapses in the striatum, where they impair neurotransmitter release and contribute to the early stages of neurodegeneration. We have generated transgenic mouse models with alpha-synuclein aggregates that reproduce the characteristic features of disease and that can be used for testing new therapeutic approaches. Alpha-synuclein aggregation is a promising target for therapy.

This talk is part of the MRC LMB Seminar Series series.

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• In person in the Max Perutz Lecture Theatre (CB2 0QH) and via Zoom link https://mrc-lmb-cam-ac-uk.zoom.us/j/98728840077?pwd=Z0MZ2xWLsyUC6fI31cIklaUbSYALwy.1
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