Recent progress on the role of GABAergic neurotransmission in the pathogenesis of Alzheimer’s disease

Abbas, G. and Mahmood, W. and Kabir, N. (2016) Recent progress on the role of GABAergic neurotransmission in the pathogenesis of Alzheimer’s disease. Reviews in the Neurosciences, 27 (4). pp. 449-455. ISSN 0334-1763

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Official URL: http://dx.doi.org/10.1515/revneuro-2015-0062

Abstract

Despite their possible causative role, targeting amyloidosis, tau phosphorylation, acetylcholine esterase, glutamate, oxidative stress and mitochondrial metabolism have not yet led to the development of drugs to cure Alzheimer's disease (AD). Recent preclinical and clinical reports exhibit a surge in interest in the role of GABAergic neurotransmission in the pathogenesis of AD. The interaction among GABAergic signaling, amyloid-β and acetylcholine is shown to affect the homeostasis between excitation (glutamate) and inhibition (GABA) in the brain. As a consequence, over-excitation leads to neurodegeneration (excitotoxicity) and impairment in the higher level functions. Previously, the glutamate arm of this balance received the most attention. Recent literature suggests that over-excitation is primarily mediated by dysfunctional GABA signaling and can possibly be restored by rectifying anomalous metabolism observed in the GABAergic neurons during AD. Additionally, neurogenesis and synaptogenesis have also been linked with GABAergic signaling. This association may provide a basis for the needed repair mechanism. Furthermore, several preclinical interventional studies revealed that targeting various GABA receptor subtypes holds potential in overcoming the memory deficits associated with AD. In conclusion, the recent scientific literature suggests that GABAergic signaling presents itself as a promising target for anti-AD drug development.

Item Type: Article
Uncontrolled Keywords: Acetylcholine; Amyloidosis; GABA; Metabolism; Neurogenesis; Synaptogenesis
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science > Institute of Biological Sciences
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 11 Oct 2017 04:08
Last Modified: 11 Oct 2017 04:08
URI: http://eprints.um.edu.my/id/eprint/17963

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