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A naturally occurring variant of SHLP2 is a protective factor in Parkinson's disease

Mol Psychiatry. 2024-01; 
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
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Peptide Synthesis SHLP2 (small humanin-like peptide 2) peptides were synthesized by Genscript (Piscataway, NJ, USA). Peptides were initially dissolved in Milli-Q water. Cycloheximide (Sigma, St. Louis, MO, USA) was used for pulse chase experiment in culture. pcDNA3.1-WT SHLP2-EGFP and pcDNA3.1-K4R SHLP2 -EGFP were cloned in Genscript (Piscataway, NJ, USA).  Get A Quote

摘要

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). Using targeted mass spectrometry, we detect specific tryptic fragments of SHLP2 in neuronal cells and demonstrate its binding to mitochondrial complex 1... More

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