ArticleAging and disease2019
The Peptide-Directed Lysosomal Degradation of CDK5 Exerts Therapeutic Effects against Stroke.
Article in Aging and disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 35 citations in OpenAlex.
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Molecular engineering of lysosome-based degraders unveils a rapidly expanding therapeutic strategy.Autophagy · 2026Review
- Exploiting targeted degradation of cyclins and cyclin-dependent kinases for cancer therapeutics: a review.Journal of Zhejiang University. Science. B · 2025Review
- Targeted protein degradation: advances in drug discovery and clinical practice.Signal transduction and targeted therapy · 2024Review
- A pan-KRAS degrader for the treatment of KRAS-mutant cancers.Cell discovery · 2024Article
- Expanding the horizons of targeted protein degradation: A non-small molecule perspective.Acta pharmaceutica Sinica. B · 2024Review
- Targeted degradation of hexokinase 2 for anti‑inflammatory treatment in acute lung injury.Molecular medicine reports · 2024Article
- Article
- Novel approaches to targeted protein degradation technologies in drug discovery.Expert opinion on drug discovery · 2023Review
- Review
- Role of cyclin-dependent kinase 5 in early brain injury following experimental subarachnoid hemorrhage.Experimental and therapeutic medicine · 2022Article
- Focusing on cyclin-dependent kinases 5: A potential target for neurological disorders.Frontiers in molecular neuroscience · 2022Review
- Targeted protein degradation in mammalian cells: A promising avenue toward future.Computational and structural biotechnology journal · 2022Review
- The role of Cdk5 in neurological disorders.Frontiers in cellular neuroscience · 2022Review
- Small molecule probes for targeting autophagy.Nature chemical biology · 2021Review
- N-Methyl-D-Aspartate Receptor Signaling-Protein Kinases Crosstalk in Cerebral Ischemia.Advances in experimental medicine and biology · 2021Article
- Proteasomal and lysosomal degradation for specific and durable suppression of immunotherapeutic targets.Cancer biology & medicine · 2020Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aberrant activation of CDK5 has been implicated in neuronal death in stroke. The goal of this study is to determine whether knocking down CDK5 by a peptide-directed lysosomal degradation approach is therapeutically effective against stroke. We synthesized a membrane-permeable peptide that specifically binds to CDK5 with a chaperone-mediated autophagy targeting motif (Tat-CDK5-CTM) and tested its therapeutic effects on a mouse model of ischemic stroke. Our results showed that Tat-CDK5-CTM blocked the CDK5-NR2B interaction, resulting in the degradation of CDK5, which in turn prevented calcium overload and neuronal death in cultured neurons. Tat-CDK5-CTM also reduced the infarction area and neuronal loss and improved the neurological functions in MCAO (Middle cerebral artery occlusion) mice. The peptide-directed lysosomal degradation of CDK5 is a promising therapeutic intervention for stroke.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.