Parkin attenuates wild-type tau modification in the presence of beta-amyloid and alpha-synuclein.
Changes in tau (tau) 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 Abeta and alpha-synuclein coexist in the brains of patients with dementia with Lewy bodies; however, it is not known how either of them interacts with tau to provoke neurofibrillary tangle formation across the tauopathies. Here, we show a role for parkin against tau pathology in the presence of intracellular Abeta or alpha-synuclein. Parkin attenuates four-repeat human tau, but not mutant P301L, hyperphosphorylation in the presence of intracellular Abeta(1-42), or alpha-synuclein and decreases GSK-3beta activity in amyloid-stressed M17 human neuroblastoma cells. These data suggest that parkin may counteract the alteration of tau metabolism in certain neurodegenerative diseases with tau cytopathy and parkinsonism.
Moussa
Charbel E-H
CE
Department of Biochemistry, Molecular and Cell Biology, Georgetown University Medical Center, The New Research Building, Room WP26B, 3970 Reservoir Rd, NW., Washington, DC 20007, USA. cem46@georgetown.edu
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D045744:Cell Line, Tumor; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D009447:Neuroblastoma; D010300:Parkinson Disease / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D024801:Tauopathies / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3