Neuroprotective Potential of Adenyl Cyclase/cAMP/CREB and Mitochondrial CoQ10 Activator in Amyotrophic Lateral Sclerosis Rats

Abstract

Aim: To investigate neuroprotective potential of Forskolin (FSK) in combination with Solanesol (SNL) along with clinically proven drugs (riluzole, baclofen, and citalopram) on behavioral, molecular and neurochemical alterations in methyl mercury-induced Amyotrophic Lateral Sclerosis (ALS) rats. Background: ALS is a motor neuron disease in which oxidative stress is the principal mechanism of neuronal death which can be mimicked by the dominant mutations in an antioxidant enzyme SOD-1. Due to MeHg neurotoxicity, behavioral and neurochemical alterations occur in rats. During ALS, mitochondrial CoQ10 dysfunctioning and downregulation of adenyl cyclase/CREB are major pathological hallmark for neurodegeneration in ALS. Clinically proven drug therapy comes with limited therapeutic involvement and is used as approachable therapy in ALS patients. Objective: Therefore, current research explores the up-regulation of adenyl cyclase/cAMP/CREB by FSK 30, 60 mg/kg in combination with mitochondrial ETC-coenzyme-Q10 precursor SNL 15, 30 mg/kg can be a preventive therapeutic approach to overcome the ALS like symptoms. Methods: MeHg (5 mg/kg) is a neurotoxic compound that leads to ALS like behavioral & neurochemical alterations. Results: Chronic treatment with the combination of FSK 30,60 mg/kg and SNL 15,30 mg/kg alone and along with standard drugs citalopram (5 mg/kg), riluzole (5 mg/kg) and baclofen (3 mg/kg) increased the adenyl cyclase and mitochondrial CoQ10 and ETC-complexes enzyme levels and shows the neuroprotective potential by significantly improving the cognitive deficitslocomotion, grip strength, and restoration of neurochemicals alterations along with reducing the level of inflammatory mediators and oxidative stress in ALS rats. Conclusion: Thus, we concluded that FSK in combination with SNL along with standard drugs can be a possible therapeutic approach for the treatment of ALS.