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GSK-3 is implicated in several diseases like Alzheimer’s disease, diabetes, mood disorders and cancer,<ref>Neurochem Res. 2007; 32(4-5): 577–595. Glycogen Synthase Kinase-3 (GSK3): Inflammation, Diseases, and Therapeutics, Richard S. Jope,* Christopher J. Yuskaitis, and Eléonore Beurel</ref>. In the Alzheimer’s disease, it is thought to be tied to the process of the hyperphosphorylation of tau proteins which leads to the formation of neurofibrillary tangles and to the build up of Amyloid-β (Aβ) deposits. Dephosphorylated tau binds normally to microtubules, one of the major components of the neuronal cytoskeleton that contributes to the proper function of neurons. | GSK-3 is implicated in several diseases like Alzheimer’s disease, diabetes, mood disorders and cancer,<ref>Neurochem Res. 2007; 32(4-5): 577–595. Glycogen Synthase Kinase-3 (GSK3): Inflammation, Diseases, and Therapeutics, Richard S. Jope,* Christopher J. Yuskaitis, and Eléonore Beurel</ref>. In the Alzheimer’s disease, it is thought to be tied to the process of the hyperphosphorylation of tau proteins which leads to the formation of neurofibrillary tangles and to the build up of Amyloid-β (Aβ) deposits. Dephosphorylated tau binds normally to microtubules, one of the major components of the neuronal cytoskeleton that contributes to the proper function of neurons. | ||
Considering the roles plaid by GSK3 in promoting both pathological features of Alzheimer disease, GSK3-inhibitors may act positively in the therapy of Alzheimer’s patients. But due to the importance of its role in numerous cellular functions, it is important to develop inhibitors that do not affect or suppress its primary activity. | Considering the roles plaid by GSK3 in promoting both pathological features of Alzheimer disease, GSK3-inhibitors may act positively in the therapy of Alzheimer’s patients. But due to the importance of its role in numerous cellular functions, it is important to develop inhibitors that do not affect or suppress its primary activity. | ||
There are two isoforms of GSK-3: GSK3α et | There are two isoforms of GSK-3: GSK3α et GSK3β . Our concern focuses on GSK3 two mechanisms that affect the activity of the kinase are its inhibition by phosphorylation of serine-9 and its activity enhancement by phosphorylation of tyrosine-216. | ||
== Activity == | == Activity == | ||
Revision as of 23:49, 30 December 2012
DescritpionDescritpion
The Glycogen Synthase Kinase 3 beta- GSK3 beta, also known as the tau protein kinase I, is a serine protein kinase that participates in many different pathways regulating critical cellular functions as structure, gene expression, mobility, and apoptosis. GSK-3 phosphorylates a large number of substrates and is himself regulated by phosphorylation. GSK-3 is implicated in several diseases like Alzheimer’s disease, diabetes, mood disorders and cancer,[1]. In the Alzheimer’s disease, it is thought to be tied to the process of the hyperphosphorylation of tau proteins which leads to the formation of neurofibrillary tangles and to the build up of Amyloid-β (Aβ) deposits. Dephosphorylated tau binds normally to microtubules, one of the major components of the neuronal cytoskeleton that contributes to the proper function of neurons. Considering the roles plaid by GSK3 in promoting both pathological features of Alzheimer disease, GSK3-inhibitors may act positively in the therapy of Alzheimer’s patients. But due to the importance of its role in numerous cellular functions, it is important to develop inhibitors that do not affect or suppress its primary activity. There are two isoforms of GSK-3: GSK3α et GSK3β . Our concern focuses on GSK3 two mechanisms that affect the activity of the kinase are its inhibition by phosphorylation of serine-9 and its activity enhancement by phosphorylation of tyrosine-216.
ActivityActivity
StructureStructure
,[2]
These are the engaged in the catalytic site of the protein, they are polar and localised in 3' end (Asp-181, Lys-183, Gln-185, Asn-186 and Ser-219. The Tau protein possesses as well as (Adenosine DiPhosphate) This enzyme is activated by phosphorylation at and inactivated by phosphorylation at Ser-9 (not shown here because this structure start at residue 35). This structure possesses 12 hydrogen bonds in order to stabilize the molecule, but in this case only four are shown (with red dashed lines) with there engaged
External RessourcesExternal Ressources
ReferencesReferences
- ↑ Neurochem Res. 2007; 32(4-5): 577–595. Glycogen Synthase Kinase-3 (GSK3): Inflammation, Diseases, and Therapeutics, Richard S. Jope,* Christopher J. Yuskaitis, and Eléonore Beurel
- ↑ http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl?pdbcode=1j1c&template=procheck_summary.html