Screening novel bile acid derived compounds for mitochondrial rescue effect in Parkinson's models

Mitochondrial dysfunction is well characterized in Parkinson’s disease. This
study aims to identify novel bile acid derived compounds, which are able to rescue mitochondrial deficits in Parkinson's models. A primary drug screen of 144 novel compounds in Parkinson’s patients’ fibroblasts, using high content imaging to determine mitochondrial membrane potential and cellular ATP assays, revealed many modified bile acids that provided mitochondrial rescue effect. Additional screening of hit compounds in a mitochondrial stress test revealed mitochondrial deficits in sporadic Parkinson's fibroblasts where hit compounds were found to restore these deficits. The top performing compound was also investigated in a MPTP mouse model where complex I, II, IV activities were assessed in ex vivo mouse brain tissue. The compound was found to be protective in this MPTP mouse model.