What is it about?
In the brain, hyperactivity of an enzyme called CDK5 is associated with neurodegenerative diseases. A new peptide that blocks the hyperactive CDK5 version produces dramatic reductions in phosphorylated tau, neurodegeneration and DNA damage in mouse models of Alzheimer’s disease pathology. It also preserved memory and cognition in lab experiments described in the paper.
Featured Image
Why is it important?
Normally, CDK5 interacts with a smaller protein called P35. The harmful hyperactive version emerges when P35 is instead cleaved into a smaller protein, P25. Pharmaceutical companies have tried to target P25/Cdk5 with small-molecule drugs, but these drugs tend to cause side effects because they also interfere with other cyclin-dependent kinases, so none of them have been tested in patients. The new peptide described in this study does not interfere with CDK1, an essential enzyme that is structurally similar to CDK5, and it is similar in size to other peptide drugs that are used in clinical applications. That makes the new peptide a potential new pathway to a viable therapy for neurodegenerative diseases such as Alzheimer’s.
Perspectives
I have been studying CDK5 ever since I discovered its activity in the brain as a postdoctoral researcher 30 years ago. I have long hoped we’d be able to develop a treatment to counter its harmful effects in the aging brain. The evidence from our experiments suggests that this new peptide has clear potential as a candidate therapeutic, which is very exciting.
Li-Huei Tsai
Massachusetts Institute of Technology
Read the Original
This page is a summary of: A Cdk5-derived peptide inhibits Cdk5/p25 activity and improves neurodegenerative phenotypes, Proceedings of the National Academy of Sciences, April 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2217864120.
You can read the full text:
Contributors
The following have contributed to this page
