Sep 21, 2022
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Newly discovered protein linked to Alzheimer’s risk

Newly discovered protein linked to Alzheimer's risk

A mutation in a newly discovered small protein is associated with a significant increase in the risk of developing Alzheimer’s disease, expanding the range of known target genes for the disease and opening up a new potential avenue for treatment, according to a new study from the University of Southern California.

The protein, called SHMOOSE, is a tiny “microprotein” encoded by a newly discovered gene in the cell’s energy-producing mitochondria. A mutation in this gene partially inactivates the SHMOOSE microprotein and is associated with a 20-50% increased risk of developing Alzheimer’s disease in four different cohorts. Nearly a quarter of people of European descent have a mutated version of the protein, according to researchers.

The results of the study were published on Wednesday, September 21 in the journal Molecular Psychiatry.

The researchers note that the significant risk and high prevalence of this previously unidentified mutation distinguishes it from other proteins involved in the development of Alzheimer’s disease. In addition to APOE4, the most powerful known genetic risk factor for disease, only a limited number of other gene mutations have been identified that increase the risk only marginally by less than 10%. In addition, since the microprotein is approximately the size of an insulin peptide, it can be easily administered, which increases its therapeutic potential.

“This discovery opens up exciting new avenues for the development of precision medicine-based therapies for Alzheimer’s disease, with SHMOOSE as the target area,” said Pinchas Cohen, professor of gerontology, medicine and life sciences and senior author of the study. “The use of SHMOOSE analogues in humans who carry the mutation and produce the mutated protein may be beneficial in neurodegenerative and other diseases of aging”

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