Calcium-dependent neutral cysteine protease and organophosphate-induced delayed neuropathy

A few organophosphorus compounds (OPs) can cause toxic neuropathy known as organophosphorus ester-induced delayed neuropathy (OPIDN). Although the incidents of OPIDN have been documented for over a century, its molecular mechanisms underlying the axonopathy are still unclear. Recently, increasing evidences suggest that proteases are closely associated with OPIDN. Herein, we have summarized the roles of calcium-dependent cysteine proteases (calpains) in OPIDN. The activation of calpains should be an early molecular event during the onset and development of OPIDN. However, the understanding of the mechanism underlying the disruption of Ca2+ homeostasis and the activation of calpain by neurotoxic OPs is still limited. Therefore, a better understanding of molecular mechanisms that can prevent the disturbance in cellular Ca2+ homeostasis can facilitate to establish the novel therapeutic strategies for OPIDN.

► There exists a significant activation of calpain in the process of OPIDN.
► Inhibition of calpain activity by drugs can alleviate clinical symptoms of OPIDN.
► Speculate activation of the proteolytic enzymes might be an early event required for the onset of OPIDN.