New Alzheimer's Disease Model Offers Hope for a New Array of Therapeutic Targets
Biomedical research is learning a great deal about how the brain works at the cellular level. Alzheimer's Disease, for example, is being seen more as an imbalance within normal cell processes -- like cancer. A better understanding of these processes should allow more precise targeting of drug research.
One of the mysteries of AD has been the normal function of the amyloid precursor protein (APP) which are concentrated at the points where neurons connect. Even though the sticky amyloid plaques which have been viewed as a hallmark sign of AD result from APP, it seems unlikely that APP exists simply to cause Alzheimer's disease. In their study, scientists from the Buck Institute and the CNRS (Centre Nationale de la Recherche Scientifique) show that APP binds to netrin-1, a protein that helps to guide nerves and their connections in the brain, as well as helping nerve cells to survive. When netrin-1 was given to mice that have a gene for Alzheimer's disease their symptoms were reversed, and the sticky amyloid was reduced. These results suggest that the long-held belief that AD is caused by brain cell damage inflicted by the amyloid plaques may be wrong; instead, it is beginning to appear that the disease stems from an imbalance between the normal making and breaking of connections in the brain, with netrin-1 supporting the connections and the amyloid breaking the connections -- both by binding to APP and activating normal cell programs. Not only did the netrin-1 binding to APP keep the nerve cells alive and connected, but it also shut down the production of the amyloid, all of which makes it an interesting potential therapeutic. _ScientistliveIn the past few decades, the therapeutic viewpoint toward Alzheimer's has paced the rapidly growing knowledge of the underlying mechanisms of the disease. Already we have gone through multiple generations of treatments, with several radically new treatments in the pipeline. If "netrin-1" or its analogues can be delivered to the proper brain regions, and can at least partially reverse both the histological and the clinical pathology in AD, we will not only have a better treatment, but we will have one more promising lead to follow.