PROTEASOME DYSFUNCTION A KEY PATHOLOGIC FEATURE OF ALZHEIMER’S DISEASE MITIGATED BY PROTEASOME ACTIVATORS
2024
Proteasome Dysfunction in Alzheimer's Disease
publication
Author Information
Author(s): Andrew Pickering
Primary Institution: University of Texas Health Science Center at Houston
Hypothesis
AD-related deficits are driven, in part, by Aβ-induced proteasome dysfunction.
Conclusion
Enhancing proteasome activity could be a promising therapeutic approach for Alzheimer's Disease.
Supporting Evidence
- Oligomeric Aβ inhibits 20S proteasome activity while destabilizing the 26S proteasome.
- Proteasome activators enhance 20S and 26S function, reducing Aβ42-induced toxicity in SK-N-SH cells.
- Oral administration of proteasome agonists delayed mortality and restored cognitive function in Drosophila overexpressing Aβ42.
- Chronic treatment with proteasome activators protected against Aβ42-induced working memory deficits in mouse models.
- Acute treatment significantly improved spatial learning deficits in hAPP(J20) mice.
Takeaway
Alzheimer's Disease can be worsened by problems with a part of the cell that helps break down waste, but we can help fix this with special treatments.
Methodology
The study involved testing proteasome activity in cell cultures and animal models after treatment with proteasome activators.
Digital Object Identifier (DOI)
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