Integrated Omics-Driven Discovery Reveals Synphilin-1-mediated Anoikis Resistance through p53 Downregulation

Synphilin-1 is a protein that interacts with α-synuclein and has been implicated in Parkinson's disease. However, the cellular and molecular mechanisms underlying the effect of synphilin-1 in Parkinson's disease remain poorly understood. This study aimed to elucidate the molecular function of synphilin-1 using integrated transcriptomic and proteomic in silico analyses, followed by in vitro validation. Synphilin-1 overexpression enhanced cell viability and attenuated pathways associated with cell death. Among the identified regulatory molecules, p53 emerged as a key mediator linking synphilin-1 to suppression of anoikis. Notably, p53 expression demonstrated predominant nuclear localisation in midbrain tissues of individuals with Parkinson's disease. These findings suggest that synphilin-1 promotes cell survival by suppressing p53-mediated anoikis. This regulatory relationship could be crucial for understanding neuroprotective or pathological mechanisms in Parkinson's disease.