4-Hydroxycinnamic acid attenuates neuronal cell death by inducing expression of plasma membrane redox enzymes and improving mitochondrial functions

Many approaches to neurodegenerative diseases that focus on amyloid-beta clearance and gene therapy have not been successful. Some therapeutic applications focus on enhancing neuronal cell survival during the pathogenesis of neurodegenerative diseases, including mitochondrial dysfunction. Plasma membrane (PM) redox enzymes are crucial in maintaining cellular physiology and redox homeostasis in response to mitochondrial dysfunction. Neurohormetic phytochemicals are known to induce the expression of detoxifying enzymes under stress conditions. In this study, mechanisms of neuroprotective effects of 4-hydroxycinnamic acid (HCA) were examined by analyzing cell survival, levels of abnormal proteins, and mitochondrial functions in two different neuronal cells. HCA protected two neuronal cells exhibited high expression of PM redox enzymes and the consequent increase in the NAD+/NADH ratio. Cells cultured with HCA showed delayed apoptosis and decreased oxidative/nitrative damage accompanied by decreased ROS production in the mitochondria. HCA increased the mitochondrial complexes I and II activities and ATP production. Also, HCA increased mitochondrial fusion and decreased mitochondrial fission. Overall, HCA maintains redox homeostasis and energy metabolism under oxidative/metabolic stress conditions. These findings suggest that HCA could be a promising therapeutic approach for neurodegenerative diseases.(c) 2023 Beijing Academy of Food Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study investigates the neuroprotective effects of 4-hydroxycinnamic acid (HCA) by analyzing cell survival, abnormal protein levels, and mitochondrial functions. The results show that HCA protects neuronal cells by increasing the expression of plasma membrane redox enzymes and improving the NAD+/NADH ratio. HCA also enhances mitochondrial activities, ATP production, and promotes mitochondrial fusion while decreasing mitochondrial fission. These findings suggest that HCA could be a promising therapeutic approach for neurodegenerative diseases.