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Tau protein and neurodegeneration
1Department of Neurology (Neuroscience), Harvard Medical School, Boston, MA.
Molecular Neurobiology
|January 1, 1990
Summary
Neurodegenerative diseases like Alzheimer's involve cytoskeleton changes, particularly with the tau protein. Abnormal tau phosphorylation leads to filamentous structures in neurons, impacting microtubule binding and solubility.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Neurodegenerative diseases often feature neuronal cytoskeleton reorganization, offering insights into disease mechanisms.
- Alzheimer's disease, a common condition, is characterized by microtubule loss and neurite accumulation of filamentous structures.
Purpose of the Study:
- To investigate the role of the microtubule-associated protein (MAP) tau in neurodegeneration.
- To understand the structural and functional changes of tau protein in Alzheimer's disease.
Main Methods:
- Analysis of tau protein expression and alternative splicing in neurons.
- Investigating tau protein phosphorylation and its impact on microtubule binding.
- Characterization of abnormal tau species (PHF-tau) in Alzheimer's brain tissue.
Main Results:
- Tau protein, encoded by a single gene, undergoes complex alternative splicing regulated by development and cell type.
- Tau protein is subject to post-translational modification, notably phosphorylation.
- Hyperphosphorylated tau protein (PHF-tau) exhibits altered solubility, fails to bind microtubules, and is found in dystrophic neurites in Alzheimer's disease.
Conclusions:
- Tau protein's altered state, particularly hyperphosphorylation, is central to the pathology of Alzheimer's disease.
- Changes in tau protein structure and function contribute to the formation of filamentous inclusions and neuronal dysfunction.