CDK5 kinase is a member of the family of cyclin-dependent kinases (CDKs) that, unlike all other members of the family, does not participate directly in cell cycle regulation. Its activity is finely regulated by its interaction with the p35 and p39 proteins. CDK5 plays a relevant role during the development of the central nervous system, its dysregulation has been implicated in different neurodegenerative diseases such as Alzheimer’s disease, amyotrophic lateral sclerosis and Parkinson’s disease, among others. This dysregulation is due in part to the cleavage of p35 to p25 induced by the activation of calpains in response to neurotoxic stress. The objective of this project is to study the participation of CDK5 in the development of neurodegenerative diseases. For this, the effect of preventing the cleavage of p35 to p25 by introducing point mutations in the cleavage site mediated by calpains, using CRISPR / Cas9 technology in neural stem cells generated from cell differentiation, will be particularly analyzed human induced pluripotent stem.
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