PIN1 Restores Phosphorylated Tau Function
In tomorrow’s issue of Nature (pp. 784-788), Kun Ping Lu of Harvard Medical School and colleagues report that an enzyme, prolyl isomerase Pin1, binds to phosphorylated tau from Alzheimer’s patients and restores tau’s ability to bind to microtubules. What’s more, levels of soluble Pin1 are reduced in the brains of Alzheimer's patients. The authors of the report note that Pin1 inhibits cells from entering mitosis, and that its depletion can induce mitotic arrest, leading to apoptotic cell death. They hypothesize that Pin1 normally acts to suppress mitosis and regulate the function of phosphoproteins such as tau, but that in Alzheimer’s disease, Pin1 becomes sequestered with the excess hyperphosphorylated tau, depleting soluble Pin1 and leading to further increases in tau hyperphosphorylation, and further depletion of Pin1.
In an accompanying News and Views article, Michel Goedert of the MRC Laboratory of Molecular Biology, Cambridge, UK, notes that “it remains to be seen whether Pin1 could restore the biological activity of tau in vivo.” If so, Pin1 could provide a new target for drug development to halt or possibly even reverse the progression of Alzheimer’s disease.—Hakon Heimer
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- Lu PJ, Wulf G, Zhou XZ, Davies P, Lu KP. The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein. Nature. 1999 Jun 24;399(6738):784-8. PubMed.
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