Cyclin-Dependent Kinase 5 (Cdk5) Inhibitory Peptide

Technology

CDK5, a tau kinase, plays essential roles in brain development and function. Under pathological conditions, aberrant CDK5 activity is mediated by p25, a proteolytic fragment of the normal activator p35, which has been implicated in numerous pathological phenotypes associated with neurodegenerative disorders. Unlike p35, p25 is not readily degraded, resulting in the constitutive activation of CDK5. This dysregulation induces various pathological phenotypes such as neuroinflammation, hyperphosphorylation of tau, and neuronal death. The present technology works by selectively blocking the interaction of CDK5 with p25, thereby preventing the formation of the complex and avoiding downstream effects, such as neuronal death, elevated amyloid β accumulation, and cognitive impairment.

Problem Addressed

The inhibition or targeted knockdown of CDK5 has been shown to relieve neurotoxicity and tau pathology in neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, spinal muscular atrophy, and frontotemporal dementia. However, previously existing drugs used to inhibit CDK5 activity have shown poor specificity, affecting the activities of basal Cdk5 and other CDKs. This off-target activity may lead to abnormal neuronal function, potentially resulting in severe side effects. The present invention offers a highly specific approach by selectively blocking the interaction between CDK5 and p25, thereby preserving basal CDK5 activity and avoiding the adverse effects associated with non-selective inhibition.  

Advantages

• Selective inhibition of the CDK/p25 complex without disrupting basal CDK5 activity
• High specificity to CDK5 without affecting other CDKs, having high homology to CDK5
• Capable of crossing the blood-brain barrier
• Broad therapeutic potential for treating neurodegenerative disorders linked to aberrant CDK5 activity