Lewy bodies: a protective response to deficient autophagy?

Daniel Erskine, Newcastle University, UK

Host: Jorge Oliveira, UCIBIO FFUP

ZOOM link: https://ucibio.pt/l/GuestSeminars

Abstract:

Lewy bodies are neuropathologically associated with Lewy body dementia (LBD), but little is known about why they form or their role in the disease process. Our research has focused on attempting to understand why Lewy bodies form and their role in the disease process. Using histology and discovery proteomics of post-mortem brain tissue, we have identified that Lewy bodies are enriched for autophagic cargo, including mitochondria decorated with ubiquitin phosphorylated at serine 65, in addition to aggresome markers. Combined with our observations of alpha-synuclein pathology in the brains of children with lysosomal storage disorders, we interpret these findings as indicating Lewy body formation may be an adaptive process to encapsulate cellular waste in the context of deficient autophagy.

Short CV:

Dr Daniel Erskine is Senior Lecturer in Neurodegenerative Pathology and head of the Metabolic Neurodegeneration Laboratory at Newcastle University, where he leads a research programme dedicated to understanding Lewy body diseases and related conditions, particularly sphingolipidoses, with a focus on metachromatic leukodystrophy and Krabbe disease. Dr Erskine’s research primarily uses post-mortem brain tissue but combines these studies with a novel in vitro platform of organotypic human brain slice cultures derived from neurosurgical patients. This work has been recognised by the awarding of two Alzheimer’s Research UK Fellowships (2019 and 2022) and the Rising Star in Lewy Body Dementia Research Gold Award in 2022.