The paper reports MTP150, a polyfunctionalized N-arylsulfonyl indole that ameliorates protein aggregation, neuroinflammation, oxidative stress, mitochondrial dysfunction, and DNA repair deficits, improving motor performance and neuroprotection in C. elegans, Drosophila, and cellular models of…

By engaging multiple PD-relevant mechanisms (aggregation, mitochondria, inflammation, DNA repair) and showing efficacy across invertebrate and cell models, MTP150 is a promising preclinical epigenetic-based lead that merits mammalian validation and translational development.

Herein, we have identified the polyfunctionalized 1-(phenylsulfonyl)-1H-indole-2-carboxylic acid derivative MTP150 for the treatment of neurodegenerative diseases owing to its efficacy in reducing protein aggregation, modulating matrix metalloproteinase activity, mitigating neuroinflammation, and enhancing DNA damage repair pathways across in vivo Caenorhabditis elegans models of Alzheimer's disease, Parkinson's disease (PD), and Huntington's disease. Further experiments in an in vivo Drosophila model of PD showed that MTP150 increased motor performance, reduced oxidative stress levels, and restored mitochondrial function in model flies. In addition, MTP150 exhibited neuroprotective effects in PD model cells, thereby supporting its therapeutic potential for this disease.