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Author Spotlight: Understanding the Impact of Pathological Proteins on Axonal Transport in Neurodegenerative Diseases
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Tau pathology-mediated presynaptic dysfunction
H Moreno1, G Morfini2, L Buitrago1
1The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Departments of Neurology and Physiology/Pharmacology, Brooklyn, NY 11203, United States; Marine Biological Laboratory, Woods Hole, MA 02543, United States.
Neuroscience
|March 26, 2016
Summary
Abnormal tau protein (htau42) in brain tauopathies disrupts synaptic transmission by altering calcium release and activating kinases like GSK3 and Cdk5, leading to neuronal dysfunction.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Brain tauopathies involve abnormal tau protein processing.
- Somatodendritic tau mislocalization is studied, but axonal tau's role is unclear.
- Previous work showed human tau (htau42) injection impairs synaptic transmission.
Purpose of the Study:
- Investigate molecular mechanisms of htau42-induced synaptic transmission failure.
- Determine the role of tau in axonal transport and neuronal connectivity.
Main Methods:
- Presynaptic microinjection of recombinant human tau protein (htau42) in squid giant synapse.
- Analysis of transmitter release and intracellular calcium dynamics.
- Use of tau-derived peptides to assess kinase involvement.
Main Results:
- htau42 injection initially increased transmitter release via calcium release.
- This was followed by a reduction in evoked transmitter release.
- A tau peptide mimicked htau42 effects, implicating phosphotransferases.
Conclusions:
- htau42 toxicity in synaptic transmission involves intracellular calcium dysregulation.
- Activation of GSK3 and Cdk5 kinases mediates htau42-induced synaptic dysfunction.
- Tau's role in axonal transport and connectivity warrants further investigation in tauopathies.
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