The latest research offers a revolutionary new model for the devastating neurodegenerative disorder Alzheimer’s, a disease that afflicts 24 million people worldwide.
In an effort to unravel the normal function of a protein implicated in Alzheimer’s, scientists in California and France have discovered a naturally occurring protein that provides a new therapeutic target for the disease. The finding is contrary to the current theory that Alzheimer’s is a disease of toxicity originating from damage caused by sticky plaques that collect in the brain.
This study from the Buck Institute for Age Research suggests Alzheimer’s as a disorder involving an imbalance in signaling between neurons.
One of the mysteries of Alzheimer’s has been the normal function of the amyloid precursor protein (APP) concentrated at the points where neurons connect. Even though the sticky amyloid plaques that have been viewed as a hallmark sign of Alzheimer’s result from APP, it seems unlikely that APP exists simply to cause Alzheimer’s.
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, as well as helping nerve cells to survive. When netrin-1 was given to mice that have a gene for Alzheimer’s their symptoms were reversed, and the sticky amyloid was reduced.
These results suggest that the long-held belief that Alzheimer’s 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.
“I think we’re going to see an explosion in the next five years involving the dissection of these signaling pathways whose imbalance leads to Alzheimer’s,” said Buck Institute Faculty Member Dale Bredesen. “We now believe that APP is part of a ‘plasticity module’ that functions in normal memory and forgetting, and that netrin-1 gives us an important starting point to restore the normal balance.”
“We believe that Alzheimer’s is somewhat analogous to cancer, which results from an imbalance between the normal processes that support cell survival and those that cause cell turnover,” said Patrick Mehlen, co-senior author of the study. “Our hope is that this research will lead to therapeutics that will be used to address this imbalance much earlier in the disease process.”
References:
1. Filipe Calheiros Lourenço, et al. Buck Institute for Age Research.
2. Image from LoreleiRanveig.
