|
23 June 1999. 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.
Reference:Lu PJ, Wulf G, Zhou XZ, Davies P, Lu KP. The prolyl isomrase Pin1 restores the function of
Alzheimer-associated phosphorylated tau prtein. Nature 1999 Jun 24;399(6738):784-8. Abstract
|
Home
The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein.
