Newly discovered genetic mutation protects against Parkinson's disease and offers hope for new therapies

A new study by the USC Leonard Davis School of Gerontology has discovered an unidentified genetic mutation in a microprotein known as SHLP2, offering a substantial shield from Parkinson's disease. The discovery offers promising new possibilities for researching possible treatments for the disease. The genetic mutation is most commonly found in individuals of European descent. This particular variant of the protein drastically lowers the risk of Parkinson's disease by 50%.

The protein SHLP2, first explored by Pinchas Cohen at USC Leonard Davis School in 2016, originates from the cell's mitochondria. Prior studies from Cohen's team established that SHLP2 levels fluctuated in patients diagnosed with Parkinson's disease. There was an increase as the body tried to resist the disease's effects, although it often failed to maintain this production as the disease further materialized. This newly discovered data compliments previous mitochondrial studies, helping broaden the research scope to include longevity, precision health, and microprotein discovery.

The leading researcher, Professor Su Jeong Kim, coordinated numerous experiments utilizing a Lab-created microprotein discovery pipeline starting with a comprehensive data-driven examination to identify disease-related variants. Thousands of participants from multiple health studies were screened for the SHLP2 variant. The research uncovered a variant in 1% of Europeans that effectively halves the risk for Parkinson's disease.

The variant results in modifications to the amino acid sequence and structure of the SHLP2 protein. Notably, the variant has enhanced stability when compared to the more common type and exhibits improved protection against mitochondrial dysfunction. SHLP2 was found binding stably to a vital mitochondrial enzyme termed mitochondrial complex 1. Its deceleration has been linked to not only Parkinson's but strokes and heart attacks as well. Given the increased stability of the SHLP2 variant, it offers superior protection to the enzyme.

Both in vitro human tissue sample experiments and mouse models of Parkinson's disease revealed the benefits of the SHLP2 mutation. Co researchers working on the study included professionals from various institutions, including USC, the National Institutes of Health, and Boston University.

More information about the complete study is available in the journal Molecular Psychiatry.