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Looking at Alzheimer's Disease Pathogenesis from the Nuclear Side
Laura D'Andrea1, Ramona Stringhi1, Monica Di Luca1
1Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy.
Biomolecules
|September 28, 2021
Summary
Alzheimer's disease players like amyloid-beta and tau protein are found in the cell nucleus. These molecules regulate gene expression, offering new therapeutic targets for Alzheimer's disease (AD).
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Alzheimer's disease (AD) is the most common dementia, characterized by amyloid-beta plaques and tau tangles.
- Key proteins in AD pathogenesis include amyloid precursor protein (APP), its metabolites like amyloid-beta (Aβ) and APP intracellular domain (AICD), and tau.
- The apolipoprotein E ε4 (APOE ε4) allele is the primary genetic risk factor for AD.
Purpose of the Study:
- To review recent advancements in how Alzheimer's disease-related molecules influence gene expression.
- To explore the nuclear functions of Aβ, tau, AICD, and APOE ε4 in the context of AD.
- To highlight the potential of targeting nuclear functions for novel AD therapeutics.
Main Methods:
- Literature review of recent advancements in Alzheimer's disease research.
- Analysis of studies investigating the localization and function of Aβ, tau, AICD, and APOE ε4.
- Examination of evidence linking nuclear functions to AD pathogenesis and gene expression.
Main Results:
- Amyloid-beta (Aβ), tau, AICD, and APOE ε4 have been found to localize within the cell nucleus.
- These molecules play roles in regulating the transcription of various genes.
- Some of the genes regulated by these nuclear proteins are implicated in Alzheimer's disease pathogenesis.
Conclusions:
- Nuclear functions are compromised in Alzheimer's disease.
- Aβ, tau, AICD, and APOE ε4 can directly modulate gene expression within the nucleus.
- Targeting these nuclear roles presents a promising avenue for developing new therapeutic strategies for Alzheimer's disease.
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