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Dephosphorylation of tau protein from Alzheimer's disease patients
K Szücs1, M D Ledesma, V Dombrádi
1Department of Medical Chemistry, University School of Medicine, Debrecen, Hungary.
Abstract:
Tau protein-prepared post-mortem from brains of Alzheimer's disease patients was treated with protein phosphatase 1 catalytic subunit, 2A catalytic subunit, and 2B (calcineurin). Dephosphorylation was monitored by immunoblotting with two monoclonal antibodies, TAU-1 and SMI31, which recognize in tau the dephospho- and phospho-states, respectively, of proline-directed protein kinase phosphorylation sites. Out of the three enzymes tested, protein phosphatase 2A was only effective in dephosphorylating tau at these Alzheimer-type epitopes.
Insights
Protein phosphatase 2A effectively dephosphorylated tau protein from Alzheimer's disease brains. This finding is crucial for understanding tau pathology and developing targeted therapies for Alzheimer's disease.
Area of Science:
- Neuroscience
- Biochemistry
- Molecular Biology
Background:
- Alzheimer's disease (AD) is characterized by the accumulation of hyperphosphorylated tau protein in neurofibrillary tangles.
- Understanding the enzymes involved in tau dephosphorylation is critical for elucidating AD pathogenesis.
Purpose of the Study:
- To investigate the efficacy of different protein phosphatases in dephosphorylating tau protein isolated from Alzheimer's disease brains.
- To identify specific phosphatases that target Alzheimer's disease-associated tau phosphorylation sites.
Main Methods:
- Post-mortem tau protein from Alzheimer's disease brains was treated with protein phosphatase 1, 2A, and 2B (calcineurin).
- Dephosphorylation was assessed using immunoblotting with TAU-1 and SMI31 monoclonal antibodies, which detect dephosphorylated and phosphorylated tau, respectively.
Main Results:
- Protein phosphatase 2A (PP2A) was the only enzyme tested that effectively dephosphorylated tau at proline-directed protein kinase phosphorylation sites.
- TAU-1 and SMI31 antibodies confirmed the specific dephosphorylation of Alzheimer's-type tau epitopes by PP2A.
Conclusions:
- Protein phosphatase 2A plays a significant role in regulating tau phosphorylation in Alzheimer's disease.
- Targeting PP2A activity could be a potential therapeutic strategy for Alzheimer's disease.