Neuroprotective Efficacy of Withaferin a On Ageing Mediated Dopaminergic Neurodegeneration An Experimental Study

Abstract

Ageing is a process characterized by a slow and gradual decline in the physiological functioning of an individual, physical frailty, motor and cognitive impairments. Degenerative ageing process is the critical cause for various non-communicable ailments like stroke, ischemic cardiovascular disorders, cancer, noninsulin-dependent diabetes mellitus, and neurodegenerative disorders. The brain succumbs to degenerative ageing process readily than any other organ, and more specifically substantia nigra pars compacta (SNpc) in the tectum of the midbrain is more vulnerable. Hence, dopamine synthesis in SNpc and thereby its functions are affected in ageing. Substantia nigra projects its neurons to caudate and putamen nuclei (striatum) forming the nigrostriatal dopaminergic system that plays a vital role in voluntary movement control. Interestingly, the SNpc neuronal loss and concurrent dysfunction of the nigrostriatal dopaminergic system is the primary characteristic of Parkinson s disease (PD). The degenerative ageing process is therefore regarded as a predisposing factor to develop PD. Hence, studying how ageing cause anatomical, physiological, and biochemical alterations in striatum (ST) and substantia nigra (SN) in nonpathological old animal models might provide valuable data. Furthermore, PD is still considered as a noncurable disease because its treatment is symptomatic. Since dopamine is ineffective at crossing the blood-brain barrier, the motor impairments of PD are treated with a dopamine precursor called L-Dopa, which readily enters the brain and converts into dopamine. The agonists for dopamine and inhibitors of monoamine oxidase B enzyme (MAOB) have also been used as drugs to treat PD symptoms. However, all these drugs on long term usage pose further clinical challenges in the late stage of PD like dyskinesia, motor fluctuations, and neuropsychiatric disorders. Further, extensive research has been carried out in animals and clinical trials to explore the neuroprotective potential of fetal dopamine cell transpl