Lombardo Sylvia, Maskos Uwe
Département de Neuroscience, Institut Pasteur, Unité Neurobiologie Intégrative des Systèmes Cholinergiques, Paris Cedex 15, France; CNRS, UMR 3571, Paris, France.
Département de Neuroscience, Institut Pasteur, Unité Neurobiologie Intégrative des Systèmes Cholinergiques, Paris Cedex 15, France; CNRS, UMR 3571, Paris, France.
Neuropharmacology. 2015 Sep;96(Pt B):255-62. doi: 10.1016/j.neuropharm.2014.11.018. Epub 2014 Dec 13.
Alzheimer's Disease (AD) is the major form of senile dementia, characterized by neuronal loss, extracellular deposits, and neurofibrillary tangles. It is accompanied by a loss of cholinergic tone, and acetylcholine (ACh) levels in the brain, which were hypothesized to be responsible for the cognitive decline observed in AD. Current medication is restricted to enhancing cholinergic signalling for symptomatic treatment of AD patients. The nicotinic acetylcholine receptor family (nAChR) and the muscarinic acetylcholine receptor family (mAChR) are the target of ACh in the brain. Both families of receptors are affected in AD. It was demonstrated that amyloid beta (Aβ) interacts with nAChRs. Here we discuss how Aβ activates or inhibits nAChRs, and how this interaction contributes to AD pathology. We will discuss the potential role of nAChRs as therapeutic targets. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'.
阿尔茨海默病（AD）是老年性痴呆的主要形式，其特征为神经元丢失、细胞外沉积物和神经原纤维缠结。它伴随着胆碱能张力丧失以及大脑中乙酰胆碱（ACh）水平下降，据推测这是导致AD患者认知衰退的原因。目前的药物治疗仅限于增强胆碱能信号传导以对AD患者进行对症治疗。烟碱型乙酰胆碱受体家族（nAChR）和毒蕈碱型乙酰胆碱受体家族（mAChR）是大脑中ACh的作用靶点。这两类受体在AD中均受到影响。已证实β-淀粉样蛋白（Aβ）与nAChRs相互作用。在此我们讨论Aβ如何激活或抑制nAChRs，以及这种相互作用如何导致AD病理变化。我们还将讨论nAChRs作为治疗靶点的潜在作用。本文是名为“烟碱型乙酰胆碱受体：从分子生物学到认知”的特刊的一部分。
