Su-Jeong Kim, Brendan Miller, Nicolas G Hartel, Ricardo Ramirez, Regina Gonzalez Braniff, Naphada Leelaprachakul, Amy Huang, Yuzhu Wang, Thalida Em Arpawong, Eileen M Crimmins, Penglong Wang, Xianbang Sun, Chunyu Liu, Daniel Levy, Kelvin Yen, Giselle M Petzinger, Nicholas A Graham, Michael W Jakowec, Pinchas Cohen
Mitochondrial DNA single nucleotide polymorphisms (mtSNPs) have been associated with a reduced risk of developing Parkinson's disease (PD), yet the underlying mechanisms remain elusive. In this study, we investigate the functional role of a PD-associated mtSNP that impacts the mitochondrial-derived peptide (MDP) Small Humanin-like Peptide 2 (SHLP2). We identify m.2158 T > C, a mtSNP associated with reduced PD risk, within the small open reading frame encoding SHLP2. This mtSNP results in an alternative form of SHLP2 (lysine 4 replaced with arginine; K4R)...
January 3, 2024: Molecular Psychiatry