Sandbox 210: Difference between revisions
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CDK5 is in several aspects important for neuronal development. It is implicated in cytoskeleton assembly and organization during axonal growth, neuronal differentiation and migration, synaptic activities in mature neurons and cell death in neurodegenerative diseases. CDK5 is also involved in the regulation of exocytosis and endocytosis of synaptic vesicles. It modulates signal transduction pathways regulating neuronal survival.<ref>PMID: 11248668</ref> CDK5 is implicated in Alzheimer’s disease as it is involved in the hyperphosphorylation of the protein Tau that leads to neuronal cell death. | CDK5 is in several aspects important for neuronal development. It is implicated in cytoskeleton assembly and organization during axonal growth, neuronal differentiation and migration, synaptic activities in mature neurons and cell death in neurodegenerative diseases. CDK5 is also involved in the regulation of exocytosis and endocytosis of synaptic vesicles. It modulates signal transduction pathways regulating neuronal survival.<ref>PMID: 11248668</ref> CDK5 is implicated in Alzheimer’s disease as it is involved in the hyperphosphorylation of the protein Tau that leads to neuronal cell death. | ||
===CDK5-p25 complex Control=== | ===CDK5-p25 complex Control=== | ||
Sometimes, p35, an activator of CDK5, is cleaved in p25 by a protease calcium-dependent, the calpain. This cut form of p35 (p25) is able to activate CDK5 and to trigger a modification of its cellular localization. It can increase its activity too. In Alzheimer’s disease or in the amyotrophic lateral sclerosis, when the ratio of p25 over p35 increases, it leads to hyperactivity of CDK5 which could hyperphosphorylate the protein Tau. The neurotoxic activator p25 activates CDK5 in one step by tethering the T-loop in the extended conformation and exposing CDK5's active site for kinase activity. When activated by p25, CDK5 causes the death of neurons, leading to neurodegenerative diseases. Deregulation of CDK5 has been implicated in Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, Huntington’s disease and acute neuronal injury. Regulators of CDK5 activity are considered as potential therapeutic molecules for degenerative diseases.<ref name="un" /> | Sometimes, p35, an activator of CDK5, is cleaved in p25 by a protease calcium-dependent, the calpain. This cut form of p35 (p25) is able to activate CDK5 and to trigger a modification of its cellular localization. It can increase its activity too. In Alzheimer’s disease or in the amyotrophic lateral sclerosis (ALS), when the ratio of p25 over p35 increases, it leads to hyperactivity of CDK5 which could hyperphosphorylate the protein Tau. The neurotoxic activator p25 activates CDK5 in one step by tethering the T-loop in the extended conformation and exposing CDK5's active site for kinase activity. When activated by p25, CDK5 causes the death of neurons, leading to neurodegenerative diseases. Deregulation of CDK5 has been implicated in Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, Huntington’s disease and acute neuronal injury. Regulators of CDK5 activity are considered as potential therapeutic molecules for degenerative diseases.<ref name="un" /> | ||
==External Resource== | ==External Resource== | ||
