title: Role of synaptic activity in the regulation of amyloid beta levels in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the most common form of dementia. Accumulation of amyloid-beta (Aβ) peptides is regarded as the critical component associated with AD pathogenesis, which is derived from the amyloid precursor protein (APP) cleavage. Recent studies suggest that synaptic activity is one of the most important factors that regulate Aβ levels. It has been found that synaptic activity facilitates APP internalization and influences APP cleavage. Glutamatergic, cholinergic, serotonergic, leptin, adrenergic, orexin, and gamma-amino butyric acid receptors, as well as the activity-regulated cytoskeleton-associated protein (Arc) are all involved in these processes. The present review summarizes the evidence for synaptic activity-modulated Aβ levels and the mechanisms underlying this regulation. Interestingly, the immediate early gene product Arc may also be the downstream signaling molecule of several receptors in the synaptic activity-modulated Aβ levels. Elucidating how Aβ levels are regulated by synaptic activity may provide new insights in both the understanding of the pathogenesis of AD and in the development of therapies to slow down the progression of AD.
authors.affiliation: Department of Physiology, Third Military Medical University, Chongqing, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Physiology, Third Military Medical University, Chongqing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institute of Geriatrics, General Hospital of Chinese PLA, Beijing, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Geng
authors.affiliation: Department of Physiology, Third Military Medical University, Chongqing, China. Electronic address: xiongjiaxiang@gmail.com.
authors.forename: Jiaxiang
authors.initials: J
authors.lastname: Xiong
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000502:physiology; D055808:Drug Discovery; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000502:physiology; D011950:Receptors, Cholinergic / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011950:Receptors, Cholinergic; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C092069:activity regulated cytoskeletal-associated protein; D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer's disease; Amyloid precursor protein; Amyloid-beta; Synaptic activity