Abstract
Changes in tau (τ) metabolism comprise important pathological landmarks in the tauopathies with parkinsonism as well as Parkinson’s disease and Alzheimer’s disease. Mutations in the parkin gene are associated with Parkinson’s disease. Deposits of amyloid proteins, including Aβ and α-synuclein coexist in the brains of patients with dementia with Lewy bodies; however, it is not known how either of them interacts with τ to provoke neurofibrillary tangle formation across the tauopathies. Here, we show a role for parkin against τ pathology in the presence of intracellular Aβ or α-synuclein. Parkin attenuates four-repeat human τ, but not mutant P301L, hyperphosphorylation in the presence of intracellular Aβ1–42, or α-synuclein and decreases GSK-3β activity in amyloid-stressed M17 human neuroblastoma cells. These data suggest that parkin may counteract the alteration of τ metabolism in certain neurodegenerative diseases with τ cytopathy and parkinsonism.