Maryland researcher finds connection between ubiquilin and Alzheimer's

In studies reported in the November Journal of Cell Biology, researchers from the University of Maryland Biotechnology Institute (Baltimore) report that ubiquilin controls levels of presenilins, proteins that are central to the early development of Alzheimer's disease. The authors say that this discovery may provide an important way to control the activity of these proteins, and potentially prevent early onset Alzheimer's disease.

Mervyn Monteiro, research professor with UMBI's Medical Biotechnology Institute, and coworkers at Case Western Reserve University, found ubiquilin to be expressed in neurons of human brain and associated with tangles and plaques in neurons of brains that are afflicted with Alzheimer's and Parkinson's diseases, respectively.

"Ubiquilin is the first molecule, to our knowledge, that has been found to increase presenilin levels in cells," said Monteiro. "Now, we want to see how ubiquilin regulates presenilin proteins carrying Alzheimer's disease mutations. This is an important step in understanding presenilins and may lead to eventual treatments or cures for the neuropathological diseases."

Previous studies have linked early-onset Alzheimer's disease to mutations in three genes: amyloid precursor protein, presenilin-1, and presenilin-2. However, the reasons why mutations in the genes cause Alzheimer's disease has not yet been fully resolved, said Monteiro. To find the latest clues, the researchers used immunonoprecipitation and yeast two-hybrid traps to show that ubiquilin is co-localized with both presenilin-1 and-2.

And while ubiquilin contains segments that target proteins for degradation, and might be viewed as a good association in terms of clearing the brain of plaque-causing protein, in this instance, ubiquilin rather seems to promotes aggregation, with no apparent affect on turn-over.

The article further explains that modulation of presenilin levels by ubiquilin may have important consequences to many cellular functions, because presenilins have been linked to various biological processes, including calcium regulation, apoptosis (programmed cell death), cell cycle regulation, and other cellular developmental functions.

For more information: Mervyn Monteiro ,Medical Biotechnology Center, University of Maryland Biotechnology Institute, 725 West Lombard St., Baltimore, MD 21201. Tel: 410-706-8132. Fax: 410-706-1732. Email: monteiro@umbi.umd.edu.

Edited by Laura DeFrancesco
Managing Editor, Bioresearch Online
ldefrancesco@bioresearchonline.com

Click here for more Alzheimer's-related research reported earlier this month at the Society for Neuroscience Annual Meeting.