A powerful predictor of Alzheimer's
SHMOOSE is a protein encoded by a newly discovered gene in mitochondrial DNA. A mutation in this gene leads to protein inactivation and is associated with a 20-50% increased risk of developing Alzheimer's disease in four different cohorts. According to researchers, almost a quarter of people of European descent have a mutated version of this protein.
The significant risk and high prevalence of this previously unidentified mutation equate it with APOE4, the most powerful known genetic risk factor for Alzheimer's disease. The remaining identified mutations increase the risk by less than 10%. The introduction of SHMOOSE analogues to people who are carriers of the mutation and produce a mutant protein may be useful in neurodegenerative and other age-related diseases. In addition, since SHMOOSE is similar in size to an insulin molecule, it is easy to inject into the body, which increases the potential for possible treatment.
Using big data methods, the researchers identified genetic variations of mitochondrial DNA associated with the risk of Alzheimer's disease. After it was discovered that mutation of the SHMOOSE gene increases the risk of developing Alzheimer's disease, brain atrophy and energy metabolism disorders, researchers began to study mutated and healthy forms of this protein.
The SHMOOSE protein appears to alter energy signaling and metabolism in the central nervous system. It was found in the mitochondria of neurons, and its levels in cerebrospinal fluid correlated with biomarkers of Alzheimer's disease. Various experiments on cell cultures and animals have shown that SHMOOSE partially alters the energy metabolism in the brain.
The obtained results emphasize the importance of a relatively new field of study of microproteins. For decades, scientists have mainly considered a set of 20,000 large genes encoding proteins. However, the new technology has identified hundreds of thousands of potential genes that encode smaller structures – microproteins.
Over the past few years, the research team has discovered several mitochondrial microproteins, including humanin, small humanin-like peptides, and the microprotein MOTS-c, which has undergone clinical trials to combat obesity and fatty liver dystrophy.
Article by B.Miller et al. Mitochondrial DNA variation in Alzheimer's disease reveals a unique microprotein called SHMOOSE published in the journal Molecular Psychiatry.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on USC Leonard Davis: Newly discovered protein connected to Alzheimer's disease risk.