Daily Archives: August 15, 2019

New Theory To Prevent Alzheimer’s

Alzheimer’s disease, the most common cause of dementia among the elderly, is characterized by plaques and tangles in the brain, with most efforts at finding a cure focused on these abnormal structures. But a University of California, Riverside, research team has identified alternate chemistry that could account for the various pathologies associated with the diseasePlaques and tangles have so far been the focus of attention in this progressive disease that currently afflicts more than 5.5 million people in the United States. Plaques, deposits of a protein fragment called beta-amyloid, look like clumps in the spaces between neurons. Tangles, twisted fibers of tau, another protein, look like bundles of fibers that build up inside cells.

The dominant theory based on beta-amyloid buildup has been around for decades, and dozens of clinical trials based on that theory have been attempted, but all have failed,” said Ryan R. Julian, a professor of chemistry who led the research team. “In addition to plaques, lysosomal storage is observed in brains of people who have Alzheimer’s disease. Neurons — fragile cells that do not undergo cell division — are susceptible to lysosomal problems, specifically, lysosomal storage, which we report is a likely cause of Alzheimer’s disease.”

An organelle within the cell, the lysosome serves as the cell’s trashcan. Old proteins and lipids get sent to the lysosome to be broken down to their building blocks, which are then shipped back out to the cell to be built into new proteins and lipids. To maintain functionality, the synthesis of proteins is balanced by the degradation of proteins.

The lysosome, however, has a weakness: If what enters does not get broken down into little pieces, then those pieces also can’t leave the lysosome. The cell decides the lysosome is not working and “stores it, meaning the cell pushes the lysosome to the side and proceeds to make a new one. If the new lysosome also fails, the process is repeated, resulting in lysosome storage.

The brains of people who have lysosomal storage disorder, another well-studied disease, and the brains of people who have Alzheimer’s disease are similar in terms of lysosomal storage,” Julian said. “But lysosomal storage disorder symptoms show up within a few weeks after birth and are often fatal within a couple of years. Alzheimer’s disease occurs much later in life. The time frames are, therefore, very different.”

Julian’s collaborative team of researchers in the Department of Chemistry and the Division of Biomedical Sciences at UC Riverside posits that long-lived proteins, including beta-amyloid and tau, can undergo spontaneous modifications that can make them undigestible by the lysosomes. “Long-lived proteins become more problematic as we age and could account for the lysosomal storage seen in Alzheimer’s, an age-related disease,” Julian said. “If we are correct, it would open up new avenues for treatment and prevention of this disease.”

Study results appear in ACS Central Science, a journal of the American Chemical Society.

Source: https://news.ucr.edu/