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- Title
The Peptide-Directed Lysosomal Degradation of CDK5 Exerts Therapeutic Effects against Stroke.
- Authors
Ya-Fan Zhou; Jing Wang; Man-Fei Deng; Bin Chi; Na Wei; Jian-Guo Chen; Dan Liu; Xiaoping Yin; Youming Lu; Ling-Qiang Zhu
- 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.
- Subjects
BIODEGRADATION; PEPTIDES; THROMBOLYTIC therapy; GLUCOSE
- Publication
Aging & Disease, 2019, Vol 10, Issue 5, p1140
- ISSN
2152-5250
- Publication type
Article
- DOI
10.14336/AD.2018.1225