Commonly associated with Alzheimer’s disease, amyloid precursor protein (APP) is now also predicted to play a role in maintaining eye health. A study from MassGeneral Institute for Neurodegenerative Disease at Massachusetts General Hospital found that two proteins binding to APP are protective against cataracts, as their deletion leads to cataract formation.
“From this kind of very basic research, we may be able to find more clues for the causes of, and ultimately to discover effective treatments for related human diseases such as cataract, congenital muscular dystrophies and Alzheimer’s disease,” said Jaehong Suh, PhD, lead author of the study that described the findings, in a news release from MassGeneral.
In piecing together the clues for the role APP plays in cataract formation, the researchers discovered that two proteins, FE65 and FE65L1, bind to APP. When the team induced a genetic mutation in mice that caused deletion of FE65 and FE65L1, mutated animals developed cataracts. This may have been the result of an alteration in the expression of the extracellular protein called laminin that under normal conditions enables an interaction between lens epithelial cells and the lens capsule.
Interestingly, the researchers noted that deletion of both FE65 and FE65L1 led to a more severe lens degeneration, whereas deletion of only FE65 or only FE65L1 was more mild. However, deletion of FE65L1 still led to cortical cataracts in old mice. “We hope the discoveries in this study would help to expand our understanding of the normal function of FE65 and APP,” said Dr. Suh. To bring light to these new findings, Dr. Suh and his colleagues published “FE65 and FE65L1 Amyloid Precursor Protein-Binding Protein Compound Null Mice Display Adult-Onset Cataract and Muscle Weakness” in The FASEB Journal.
Precisely why a protein related to Alzheimer’s disease can also be related to cataracts is still a mystery. The editor in chief of The FASEB Journal, Gerald Weissman, MD, finds the situation compelling. “It’s rare that in any living system, one gene or one protein performs only one function,” said Dr. Weissmann. “Although this is a new find, the fact that a protein implicated in Alzheimer’s disease has a function in tissues other than the brain should come as no surprise–but APP’s function in the eye is unexpected!”