Transporters as Drug Targets in Neurological Diseases

Abstract

Membrane transport proteins have central physiological function in maintaining cerebral homeostasis. These transporters are expressed in almost all cerebral cells where they regulate the movement of wide range of solutes including endogenous substrates, xenobiotic and therapeutic drugs. Altered activity/expression of CNS transporters has been implicated in the onset and progression of multiple neurological diseases. Neurological diseases are heterogeneous diseases that involve complex pathological alterations with only a few treatment options; therefore there is a great need for the development of novel therapeutic treatments. To that end, transporters have emerged recently to be promising therapeutic targets to halt or slow the course of neurological diseases. The objective of this review is to discuss implications of transporters in neurological diseases and summarize available evidence for targeting transporters as decent therapeutic approach in the treatment of neurological diseases.

Functional Expression of Organic Anion Transporting Polypeptide 1a4 Is Regulated by Transforming Growth Factor-β/Activin Receptor-like Kinase 1 Signaling at the Blood-Brain Barrier

“…The BBB is a formidable obstacle to CNS drug delivery that often renders treatment of brain diseases ineffective (Qosa et al, 2016). One such example is ischemic stroke, which is characterized by reduced oxygen and glucose supply to ischemic brain tissue (Liu et al, 2010;Brzica et al, 2017).…”

Drug Transporters: Advances and Opportunities

“…review the ramifications of brain transporters in the pathogenesis of Alzheimer disease, amyotrophic lateral sclerosis, Lewy body dementia, Parkinson disease, epilepsy, multiple sclerosis, and stroke. These authors discuss how targeting of these transporters could potentially modify the progression of disease pathogenesis and/or enhance the efficacy of drugs used to treat these conditions . Several recent advances on the exploitation of ABC and SLC transporters as therapeutic targets in the aforementioned disease conditions are presented.…”

“…Dysfunction of the brain's transporters has been linked to an array of neuropathologic conditions and in the alterations of entry or clearance of centrally acting drugs. In this issue, Qosa et al 15 review the ramifications of brain transporters in the pathogenesis of Alzheimer disease, amyotrophic lateral sclerosis, Lewy body dementia, Parkinson disease, epilepsy, multiple sclerosis, and stroke. These authors discuss how targeting of these transporters could potentially modify the progression of disease pathogenesis and/or enhance the efficacy of drugs used to treat these conditions.…”

“…These authors discuss how targeting of these transporters could potentially modify the progression of disease pathogenesis and/or enhance the efficacy of drugs used to treat these conditions. 15 Several recent advances on the exploitation of ABC and SLC transporters as therapeutic targets in the aforementioned disease conditions are presented. On the other hand, Jones and Morris 16 elaborate the role of monocarboxylate transporters in many disease processes, including neurologic conditions, such as hyperammonemia.…”

Functional Expression of P-glycoprotein and Organic Anion Transporting Polypeptides at the Blood-Brain Barrier: Understanding Transport Mechanisms for Improved CNS Drug Delivery?

“…This therapeutic objective is highly dependent upon expression and activity of transporters in brain microvascular endothelial cells. Such endogenous BBB transporters are determinants of drug disposition in the brain and, by extension, CNS drug efficacy (1). Therefore, it is critical to thoroughly study localization, regulation, and functional expression of BBB transport proteins in order to develop novel approaches for CNS drug delivery.…”