Voltage-Gated Na+ Channels in Alzheimer’s Disease: Physiological Roles and Therapeutic Potential
Author:
Baumgartner Timothy J.1ORCID,
Haghighijoo Zahra1ORCID,
Goode Nana A.1,
Dvorak Nolan M.1ORCID,
Arman Parsa1ORCID,
Laezza Fernanda1ORCID
Affiliation:
1. Department of Pharmacology & Toxicology, The University of Texas Medical Branch, Galveston, TX 77555, USA
Abstract
Alzheimer’s disease (AD) is the most common cause of dementia and is classically characterized by two major histopathological abnormalities: extracellular plaques composed of amyloid beta (Aβ) and intracellular hyperphosphorylated tau. Due to the progressive nature of the disease, it is of the utmost importance to develop disease-modifying therapeutics that tackle AD pathology in its early stages. Attenuation of hippocampal hyperactivity, one of the earliest neuronal abnormalities observed in AD brains, has emerged as a promising strategy to ameliorate cognitive deficits and abate the spread of neurotoxic species. This aberrant hyperactivity has been attributed in part to the dysfunction of voltage-gated Na+ (Nav) channels, which are central mediators of neuronal excitability. Therefore, targeting Nav channels is a promising strategy for developing disease-modifying therapeutics that can correct aberrant neuronal phenotypes in early-stage AD. This review will explore the role of Nav channels in neuronal function, their connections to AD pathology, and their potential as therapeutic targets.
Funder
National Institutes of Health
National Institute of Aging
Houston Area Molecular Biophysics Program
Subject
Paleontology,Space and Planetary Science,General Biochemistry, Genetics and Molecular Biology,Ecology, Evolution, Behavior and Systematics
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