Molecular clue to Alzheimer's mystery found

November 12, 2000

In cell biology studies, researchers report "strong evidence" that a molecule called ubiquilin controls levels of certain proteins that are central to the early development of Alzheimer's disease.

In today's Journal of Cell Biology, researchers of the University of Maryland Biotechnology Institute (UMBI) say the discovery may provide an important way to control the activity of proteins called presenilins. Previous studies showed that mutations in genes coding for presenilins cause early onset of Alzheimer's disease.

Mervyn Monteiro, research professor with UMBI's Medical Biotechnology Institute and coworkers at Case Western Reserve University, also found ubiquilin to be "highly 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."

Molecular genetic studies previously linked early-onset Alzheimer's disease to mutations in three genes: amyloid precursor protein, presenilin-1 and presenilin-2. However, the biological 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 combinations of immunological and DNA-taging methods to learn that ubiquilin is localized in both the nucleus and cytoplasm in cells.

The journal paper 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.
-end-


University of Maryland Biotechnology Institute

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