ABC Transporters in Neurological Disorders: An Important Gateway for Botanical Compounds Mediated Neuro-Therapeutics.

Abstract

Neurodegeneration is a distinguishing feature of many age related disorders and other vector borne neuroinflammatory diseases. There are a number of factors that can modulate the pathology of these disorders. ATP-binding cassette (ABC) transporters are primarily involved in the maintenance of normal brain homeostasis by eliminating toxic peptides and compounds from the brain. Also, ABC transporters protect the brain from the unwanted effects of endogenous and exogenous toxins that can enter the brain parenchyma. Therefore, these transporters have the ability to determine the pathological outcomes of several neurological disorders. For instance, ABC transporters like P-glycoprotein (ABCB1), and BCRP (ABCG2) have been reported to facilitate the clearance of peptides such as amyloid-β (Aβ) that accumulate in the brain during Alzheimer's disease (AD) progression. Other members such as ABCA1, ABCA2, ABCC8, ABCC9, ABCG1 and ABCG4 also have been reported to be involved in the progression of various brain disorders such as HIV-associated dementia, Multiple sclerosis (MS), Ischemic stroke, Japanese encephalitis (JE) and Epilepsy. However, these defective transporters can be targeted by numerous botanical compounds such as Verapamil, Berberine and Fascalpsyn as a therapeutic target to treat these neurological outcomes. These compounds are already reported to modulate ABC transporter activity in the CNS. Nonetheless, the exact mechanisms involving the ABC transporters role in normal brain functioning, their role in neuronal dysfunction and how these botanical compounds ensure and facilitate their therapeutic action in association with defective transporters still remain elusive. This review therefore, summarizes the role of ABC transporters in neurological disorders, with a special emphasis on its role in AD brains. The prospect of using botanical/natural compounds as modulators of ABC transporters in neurological disorders is discussed in the latter half of the article.