A new USC study finds that a mutation in a newly discovered small protein is connected to a significant increase in the risk for Alzheimer’s disease.risk and highlights a possible target for treatment.
Called SHMOOSE, the protein is a tiny “microprotein” encoded by a newly discovered gene within the cell’s energy-producing mitochondria. A mutation within this gene partially inactivates the SHMOOSE microprotein and is linked to a 30% higher risk for Alzheimer’s disease across four different cohorts. According to the researchers, almost 25% of people of European ancestry have the mutated version of the protein.
“This discovery opens exciting new directions for developing precision medicine-based therapies for Alzheimer’s disease, focusing on SHMOOSE as a target area,” said Pinchas Cohen. He is the senior author of the study and professor of gerontology, medicine and biological sciences. “Administration of SHMOOSE analogs in individuals who carry the mutation and produce the mutant protein may prove to have benefit in neurodegenerative and other diseases of aging.
It appears that the microprotein modifies energy signaling and metabolism in the central nervous system. It was found in mitochondria of neurons and its levels in cerebrospinal fluid correlated with biomarkers of Alzheimer’s disease. A variety of cell culture and animal experiments showed that SHMOOSE alters energy metabolism in the brain in part by inhabiting a crucial part of the mitochondria, the inner mitochondrial membrane.
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