Title : The use of cephalexin to inhibit alpha-synuclein aggregation: A new paradigm in parkinson's disease
Abstract:
Introduction: Parkinson’s Disease (PD) is characterized by the degeneration of dopaminergic neurons due to the aggregation of a protein named α-Synuclein in the substantia nigra region of the brain. Current therapies for PD do not address this pathology. This paper presents Cephalexin, an antibacterial agent as potential treatment for PD; particularly addressing α-Synuclein aggregation.
Methods: The protective effects of Cephalexin against PD were evaluated using MTT Proliferation Assays, Silica Molecular Docking, ELISA, and the D. melanogaster Climbing Assay. The results were validated using a two-tailed t-test
Results: Within 36 hrs., Cephalexin demonstrated a notable reduction in neural cell mortality induced by Rotenone, a pesticide known to induce parkinsonian symptoms in rodent models (43% to 26%, p < 0.05). Cephalexin induced the expression of PARKIN, a critical protein that plays essential roles in protein degradation and mitophagy (116%, p < 0.05). Silica Molecular Docking revealed that Cephalexin binds to α-Synuclein at the same location where α-Synuclein binds to Rotenone. In in vitro experimentation, compared to Rotenone, Cephalexin demonstrated under expression of LRP1 over both 24 hours (75.21% vs Rotenone’s 99.976%, p < 0.05) and 48 hours (-68.46% vs Rotenone’s 20.83%, p < 0.05). Finally, the in vivo D.melanogaster Climbing Assay showed that Cephalexin-treated flies climbed higher compared to the control by an average 75.52%, p < 0.05 (Day 5).
Conclusion: Cephalexin shows considerable promise - reverses the effects of Rotenone induced cytotoxicity while promoting induction of PARKIN and under expressing LRP1. D. melanogaster models further demonstrated Cephalexin’s promise as a PD treatment by showcasing its ability to enhance motor functions.
