Abstract
There remain many currently incurable diseases in which cell death is evident in the affected organs. Extensive cell death leads to impaired function of the affected organs, leading to the overt manifestation of the diseases. For example, Parkinson’s disease, the second most common neurodegenerative disorder next to Alzheimer’s disease, is caused by the death of dopaminergic neurons in the substantia nigra. On the other hand, for cells or animals to survive, abundant ATP is necessary, and the depletion of ATP levels is commonly observed in dying cells. With this in mind, we have long searched for compounds that prevent the ATP decrease in affected cells. We have successfully created small chemicals, KUSs (Kyoto University Substances) , which can reduce cellular ATP consumption. Furthermore, we found that esculetin is able to stimulate ATP production. We thus collectively refer to these compounds as "ATP regulators" . We then examined the efficacies of the ATP regulators on cell culture and mouse models of Parkinson’s disease. Both types of ATP regulators showed significant efficacies in preventing the ATP decrease, ER stress, and cell death in dopaminergic neurons. These results raise the possibility that maintenance of ATP levels by the ATP regulators could be a promising therapeutic strategy for Parkinson’s disease.
