Naturally Derived Rho‐kinase 2 Inhibitors Acting as Mitophagy Inducer: A Novel Therapeutic Approach for Alzheimer’s Disease

The aged and damaged mitochondria are removed through a selective mode of autophagy called mitophagy. The mitophagy may be triggered mainly via Parkin‐dependent and Parkin‐independent pathways. However, in different pathological conditions, this process is impaired in neuronal cells and lead to a variety of neurodegenerative disease (NDD) including Alzheimer Disease (AD). In case of AD, the pathological conditions such as accumulation of amyloid beta plaques and neurofibrillary tangles are also reported to inhibit the clearance of damaged mitochondria via the process of mitophagy. Hence triggering the mitophagy may be a promising therapeutic approach for the management of such conditions. In light of the significant role of impaired mitophagy in AD, further studies have also investigated the regulatory pathways/ protein involved in triggering mitophagy. Consequently, in the recent past Rho‐kinase 2 (ROCK) in suggested to negatively regulate the Parkin‐dependent mitophagy pathway in neuronal cells. Thus, inhibition of ROCK protein may trigger mitophagy in the treated cells and may alleviate the pathological conditions. Several synthetic compounds are studied for their ROCK2 inhibiting ability, but due to their side effects; immense attention is being diverted towards the use of natural compounds. We explored the ROCK2‐targeting ability of phytocompounds from the 7 medicinal plants (Allium sativum, Camellia sinensis, Centella asiatica, Nelumbo nucifera, Punica granatun, Rosmarinus officinalis and Triticum aestivum) used as neuro‐tonic.