p73: a multifunctional protein in neurobiology
Richard Killick1, Maria Niklison-Chirou, Richard Tomasini
1King's College London, Institute of Psychiatry, Old Age Psychiatry and Dementia, London, SE5 8AF, UK.
Molecular Neurobiology
|March 8, 2011
Summary
The p73 (p53 family transcription factor) subfamily is crucial for neuronal development and survival. Its isoforms, TAp73 and ΔNp73, are implicated in neurodevelopmental disorders and neurodegeneration, including Alzheimer's disease.
Area of Science:
- Molecular Biology
- Neuroscience
- Genetics
Background:
- The p73 transcription factor, part of the p53 family, is involved in critical biological processes.
- p73 isoforms, TAp73 and ΔNp73, have distinct roles in neuronal function.
- Dysregulation of p73 is linked to neurodevelopmental and neurodegenerative conditions.
Purpose of the Study:
- To elucidate the role of p73 isoforms in neuronal development and neurodegeneration.
- To investigate the impact of TAp73 and ΔNp73 deficiencies on neuronal pathologies.
- To explore the potential involvement of p73 in Alzheimer's disease.
Main Methods:
- Analysis of mice deficient for TAp73 and ΔNp73 isoforms.
- Examination of TAp73 expression during neuronal differentiation.
- Investigation of ΔNp73 function in mature cortical neurons.
- Review of recent evidence on p73 deregulation in neurodegenerative diseases.
Main Results:
- Mice lacking both TAp73 and ΔNp73 isoforms exhibit hydrocephalus and hippocampal dysgenesis.
- TAp73 expression correlates with neuronal differentiation, promoting neurite outgrowth.
- ΔNp73 null mice show reduced cortical thickness, indicating a survival role.
- p73 isoforms are deregulated in Alzheimer's disease, associated with abnormal tau phosphorylation.
Conclusions:
- The p73 subfamily plays a significant role in both neuronal development and neurodegeneration.
- TAp73 promotes neuronal differentiation, while ΔNp73 supports neuronal survival.
- Aberrant p73 function contributes to neurological disorders, including Alzheimer's disease.
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