Cyclin‐dependent kinase 5 (CDK5) inhibitors in Parkinson disease

• Published in: Journal of cellular and molecular medicine 2024-06, Vol.28 (11), p.e18412-n/a
• Main Authors: Alrouji, Mohammed, Al‐kuraishy, Haydar M., Al‐Gareeb, Ali I., Alshammari, Mohammed S., Alexiou, Athanasios, Papadakis, Marios, Bahaa, Mostafa M., Batiha, Gaber El‐Saber
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amino acids; Animals; Calpain; Calpain - antagonists & inhibitors; Calpain - metabolism; Cdk5 inhibitors; Cell cycle; Cell death; Central nervous system; Cyclin-dependent kinase 5; Cyclin-Dependent Kinase 5 - antagonists & inhibitors; Cyclin-Dependent Kinase 5 - metabolism; Cyclin-dependent kinases; Cytoskeleton; Disease; Dopamine; Drug abuse; Humans; Hyperactivity; Kinases; Metformin; Movement disorders; Nervous system; Neurodegeneration; Neurodegenerative diseases; Neurons; Neuropathology; Neuroprotection; Oxidative stress; Parkinson disease; Parkinson Disease - drug therapy; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Pathogenesis; Pathophysiology; Phosphorylation; Physiology; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Proteins; Regulatory subunits; Review; Reviews; Rosiglitazone; Signal Transduction - drug effects; Statins; Synaptic plasticity
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.18412

Cyclin‐dependent kinase 5 (Cdk5) is a protein expressed in postmitotic neurons in the central nervous system (CNS). Cdk5 is activated by p35 and p39 which are neuron regulatory subunits. Cdk5/p35 complex is activated by calpain protease to form Cdk5/p35 which has a neuroprotective effect by regulating the synaptic plasticity and memory functions. However, exaggerated Cdk5 is implicated in different types of neurodegenerative diseases including Parkinson disease (PD). Therefore, modulation of Cdk5 signalling may mitigate PD neuropathology. Therefore, the aim of the present review was to discuss the critical role of Cdk5 in the pathogenesis of PD, and how Cdk5 inhibitors are effectual in the management of PD. In conclusion, overactivated Cdk5 is involved the development of neurodegeneration, and Cdk5/calpain inhibitors such as statins, metformin, fenofibrates and rosiglitazone can attenuate the progression of PD neuropathology.