Hsp90 regulates tau pathology through co-chaperone complexes in Alzheimer's disease.

摘要: Alzheimer's disease is a tauopathy which involves the deposition of microtubule-associated tau proteins into neurofibrillary tangles. Post-translational modifications, in particular site-specific phosphorylations, affect conformation protein an intrinsically disordered protein. These structural changes significantly increase affinity for certain molecular chaperones. Hsp90 major cellular chaperone assembles large complexes with variety co-chaperones. The main function to maintain quality control and assist degradation via proteasomal autophagic-lysosomal pathways. Tau client these complexes. If abnormal or modified form, then it can trigger recruitment CHIP protein, co-chaperone E3 activity, complex induces ubiquitination activates its downstream processes. Large immunophilins, FKBP51 FKBP52 are also co-chaperones Hsp90-tau contain peptidylprolyl cis/trans isomerase activity catalyzes phosphorylation-dependent rotation pSer/Thr-Pro peptide bond. proline switch triggers dephosphorylation Ser/Thr residues phosphorylated, e.g. by two well-known kinases Cdk5 GSK-3β. Binding PP5 phosphatase complex, dephosphorylate Subsequently, dephosphorylated be shuttled back microtubules. It seems that high-affinity binding may have some counteracting effects on aggregation process, since inhibitors ameliorate process several neurodegenerative diseases. We will review role network regulation biology pathology disease.