cn0c00096_si_liveslides.zip (7.47 MB)
Physiological and Pathological Roles of Cdk5: Potential Directions for Therapeutic Targeting in Neurodegenerative Disease
online resource
posted on 2020-05-18, 18:38 authored by Annamarie
B. Allnutt, Ariana K. Waters, Santosh Kesari, Venkata Mahidhar YenugondaCyclin-dependent
kinase 5 (Cdk5) is a proline-directed serine (ser)/threonine
(Thr) kinase that has been demonstrated to be one of the most functionally
diverse kinases within neurons. Cdk5 is regulated via binding with
its neuron-specific regulatory subunits, p35 or p39. Cdk5–p35
activity is critical for a variety of developmental and cellular processes
in the brain, including neuron migration, memory formation, microtubule
regulation, and cell cycle suppression. Aberrant activation of Cdk5
via the truncated p35 byproduct, p25, is implicated in the pathogenesis
of several neurodegenerative diseases. The present review highlights
the importance of Cdk5 activity and function in the brain and demonstrates
how deregulation of Cdk5 can contribute to the development of neurodegenerative
conditions such as Alzheimer’s and Parkinson’s disease.
Additionally, we cover past drug discovery attempts at inhibiting
Cdk5–p25 activity and discuss which types of targeting strategies
may prove to be the most successful moving forward.