Dysfunctional synapse in Alzheimer's disease - A focus on NMDA receptors

NEUROPHARMACOLOGY

卷:76

Review

Mota, Sandra I.¹  Ferreira, Ildete L.^1,2  Cristina Rego, A.^1,2,3 

[1] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, P-3004504 Coimbra, Portugal

[2] Univ Coimbra IIIUC, Inst Interdisciplinary Res, P-3030789 Coimbra, Portugal

[3] Univ Coimbra, Fac Med, P-3000354 Coimbra, Portugal

关键词: Alzheimer's disease;    Amyloid-beta peptide;    Synaptic dysfunction;    NMDA receptors;    GluN2A and G1uN2B subunits;    Tripartite synapse;   

DOI  :  10.1016/j.neuropharm.2013.08.013

来源: Elsevier

【 摘 要 】

Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly. Alterations capable of causing brain circuitry dysfunctions in AD may take several years to develop. Oligomeric amyloid-beta peptide (AB) plays a complex role in the molecular events that lead to progressive loss of function and eventually to neurodegeneration in this devastating disease. Moreover, N-methyl-D-aspartate (NMDA) receptors (NMDARs) activation has been recently implicated in AD-related synaptic dysfunction. Thus, in this review we focus on glutamatergic neurotransmission impairment and the changes in NMDAR regulation in AD, following the description on the role and location of NMDARs at pre- and post-synaptic sites under physiological conditions. In addition, considering that there is currently no effective ways to cure AD or stop its progression, we further discuss the relevance of NMDARs antagonists to prevent AD symptomatology. This review posits additional information on the role played by All in AD and the importance of targeting the tripartite glutamatergic synapse in early asymptomatic and possible reversible stages of the disease through preventive and/or disease-modifying therapeutic strategies. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. (C) 2013 Elsevier Ltd. All rights reserved.

【 授权许可】

Free