Enzyme plays dual role in Alzheimer's

Tau proteins and amyloid-β peptides aggregate to form tangles and plaques in the brains of Alzheimer's disease patients. Back in 2003, Kun Ping Lu of Harvard Medical School showed that the enzyme Pin1 limits formation of tau tangles. Now, Lu and colleagues have found that Pin1 also curbs formation of amyloid plaques (Nature 2006, 440, 528). The group found that Pin1 binds to a phosphorylated threonine/proline segment of amyloid precursor protein in a way that favors its conversion from a cis (top) to a trans (bottom) conformation (red arrow indicates isomerized bond). The trans conformation of amyloid precursor protein is then clipped by other cellular enzymes into fragments useful for neuronal growth and survival. The cis conformation, on the other hand, is processed into fragments that include toxic amyloid-β peptides. The findings suggest that "lack of sufficient Pin1 enzyme may be a key culprit in the onset of Alzheimer's disease," Lu says.