Cell Biology

Presenilins Get a Boost

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Science  24 Nov 2000:
Vol. 290, Issue 5496, pp. 1467
DOI: 10.1126/science.290.5496.1467c

Some patients with early-onset Alzheimer's disease (AD) have mutations in the genes that encode the presenilins. These multispanning membrane proteins are essential for early development but their role in pathogenesis remains poorly understood.

Now Mah et al. have identified a human protein called ubiquilin that binds to presenilins and promotes their accumulation. The ubiquilin gene maps to a chromosomal region that is thought to contain a susceptibility gene for late-onset AD. Interestingly, although ubiquilin contains ubiquitin-related domains, which usually target proteins for degradation, it does not alter presenilin turnover but instead appears to increase presenilin synthesis. Like ubiquitin, ubiquilin is present in neuropathological lesions that are characteristic of AD (neurofibrillary tangles) and Parkinson's disease (Lewy bodies). The discovery of ubiquilin may provide a clue to a new mechanism by which presenilin levels are regulated. — PAK

J. Cell Biol. 151, 847 (2000).

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