title: Implications of GABAergic Neurotransmission in Alzheimer's Disease.
abstract: Alzheimer's disease (AD) is characterized pathologically by the deposition of β-amyloid peptides (Aβ) and the accumulation of neurofibrillary tangles (NFTs) composed of hyper-phosphorylated tau. Regardless of the pathological hallmarks, synaptic dysfunction is widely accepted as a causal event in AD. Of the two major types of synapses in the central nervous system (CNS): glutamatergic and GABAergic, which provide excitatory and inhibitory outputs respectively, abundant data implicate an impaired glutamatergic system during disease progression. However, emerging evidence supports the notion that disrupted default neuronal network underlies impaired memory, and that alterations of GABAergic circuits, either plays a primary role or as a compensatory response to excitotoxicity, may also contribute to AD by disrupting the overall network function. The goal of this review is to provide an overview of the involvement of Aβ, tau and apolipoprotein E4 (apoE4), the major genetic risk factor in late-onset AD (LOAD), in GABAergic neurotransmission and the potential of modulating the GABAergic function as AD therapy.
authors.affiliation: Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University Xiamen, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University Xiamen, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.affiliation: Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University Xiamen, China.
authors.forename: Zhicai
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen UniversityXiamen, China; Neurodegenerative Disease Research Program, Sanford-Burnham Medical Research InstituteLa Jolla, CA, USA.
authors.forename: Huaxi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen UniversityXiamen, China; Department of Neuroscience, Mayo ClinicJacksonville, FL, USA.
authors.forename: Guojun
authors.initials: G
authors.lastname: Bu
authors.affiliation: Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen UniversityXiamen, China; The Interdepartmental Program of Translational Biology and Molecular Medicine, Huffington Center on Aging, Baylor College of MedicineHouston, TX, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
keywords: GABAergic neurotransmission; amyloid beta-peptides; apolipoproteins E; neuronal inhibition; tau proteins