Proteomic analysis of human iPSC-derived sympathetic neurons identifies proteostasis collapse as a molecular signature following subtoxic rotenone exposure.

Rotenone is a toxic isoflavone and an inhibitor of the mitochondrial respiratory chain. Rotenone is commonly used due to its piscicidal and pesticidal properties. The peripheral nervous system (PNS) lacks protective barriers and is exposed to many environmental substances due to its long-reaching structure.

Chronic and acute exposure to rotenone reveals distinct Parkinson's disease-related phenotypes in human iPSC-derived peripheral neurons.

Peripheral autonomic nervous system (P-ANS) dysfunction is a critical non-motor phenotype of Parkinson's disease (PD). The majority of PD cases are sporadic and lack identified PD-associated genes involved. Epidemiological and animal model studies suggest an association with pesticides and other environmental toxins.

4-Phenylbutyric Acid (4-PBA) Derivatives Prevent SOD1 Amyloid Aggregation In Vitro with No Effect on Disease Progression in SOD1-ALS Mice.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the degeneration of motor neurons. Mutations in the superoxide dismutase (SOD1) gene, causing protein misfolding and aggregation, were suggested as the pathogenic mechanisms involved in familial ALS cases. In the present study, we investigated the potential therapeutic effect of C4 and C5, two derivatives of the chemical chaperone 4-phenylbutyric acid (4-PBA).