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Dysfunctional protein in neurons causes build-up, spread of Lewy body clumps


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Journal
Journal of Neuroscience
Reuters Health - 07/03/2022 - Toxins could cause a key autophagy-related protein in neurons to malfunction, triggering the build-up and spread from cell to cell of protein clumps that are hallmarks of Parkinson's Disease (PD), Lewy body dementia (LBD), and other neurodegenerative disorders, according to a new study.  In a series of laboratory experiments, researchers tracked the role of the p62 protein, showing how its aberrant modification by nitric oxide (NO) leads to inhibition of autophagy, a cellular disposal process that "eats" dysfunctional proteins and organelles. The authors also show how that inhibition, in turn, causes build-up and then secretion of misfolded alpha-synuclein and other proteins that p62 would normally have marked for destruction.


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