Alzheimer's disease: An evolving understanding of noradrenergic involvement and the promising future of electroceutical therapies.
Alzheimer's disease: An evolving understanding of noradrenergic involvement and the promising future of electroceutical therapies.
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DOI：
10.1002/ctm2.397
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发表时间：
2021-04
影响因子：
10.6
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Slater C;Wang Q
阿尔茨海默氏病（AD）在未来几十年内构成了一个重大的全球健康问题。已经提出了多种假说，试图解释AD的潜在病理生理学。这里简要回顾了其中的许多方法，但迄今为止还没有实现改变疾病的治疗。尽管如此，最近的工作扩大的作用，去甲肾上腺素能系统功能障碍的发病机制和症状恶化的AD已显示出希望。去甲肾上腺素（NE）在AD中的作用仍然很复杂，但在症状发作前数十年，AD患者的蓝斑（LC）中一直显示出预缠结tau蛋白。本文回顾的当前研究表明，NE可以通过β肾上腺素能受体促进神经保护和记忆增强作用，而α2A肾上腺素能受体可能通过促进tau过度磷酸化而加剧淀粉样蛋白毒性。AD似乎涉及这两种受体及其各种亚型之间平衡的破坏。去甲肾上腺素能和胆碱能系统之间的相互作用也很难描述。LC恶化导致剩余LC-NE系统适应不良，随后抑制胆碱能神经元功能，最终导致AD中观察到的经典胆碱能破坏。了解AD作为一个功能失调的去甲肾上腺素能系统，提供了新的途径，使用先进的神经刺激技术，研究和治疗目标的最早阶段的神经病理学。直接LC刺激和无创迷走神经刺激（VNS）均已证明可用作AD治疗剂。然而，为了更好地理解去甲肾上腺素能系统在AD中的作用以及电化学药物如何提供改变疾病的治疗，仍有重要的工作要做。在这篇综述中，我们简要概述了几个研究最彻底的阿尔茨海默病（AD）致病假设，并评估其临床影响。我们特别关注最近对蓝斑去甲肾上腺素（LC-NE）系统在AD发病机制和症状加重中的作用的研究，以及在神经病理学的最早阶段使用先进的神经刺激技术作为新的治疗选择的潜力。
Alzheimer's disease (AD) poses a significant global health concern over the next several decades. Multiple hypotheses have been put forth that attempt to explain the underlying pathophysiology of AD. Many of these are briefly reviewed here, but to‐date no disease‐altering therapy has been achieved. Despite this, recent work expanding on the role of noradrenergic system dysfunction in both the pathogenesis and symptomatic exacerbation of AD has shown promise. The role norepinephrine (NE) plays in AD remains complicated but pre‐tangle tau has consistently been shown to arise in the locus coeruleus (LC) of patients with AD decades before symptom onset. The current research reviewed here indicates NE can facilitate neuroprotective and memory‐enhancing effects through β adrenergic receptors, while α2A adrenergic receptors may exacerbate amyloid toxicity through a contribution to tau hyperphosphorylation. AD appears to involve a disruption in the balance between these two receptors and their various subtypes. There is also a poorly characterized interplay between the noradrenergic and cholinergic systems. LC deterioration leads to maladaptation in the remaining LC‐NE system and subsequently inhibits cholinergic neuron function, eventually leading to the classic cholinergic disruption seen in AD. Understanding AD as a dysfunctional noradrenergic system, provides new avenues for the use of advanced neural stimulation techniques to both study and therapeutically target the earliest stages of neuropathology. Direct LC stimulation and non‐invasive vagus nerve stimulation (VNS) have both demonstrated potential use as AD therapeutics. Significant work remains, though, to better understand the role of the noradrenergic system in AD and how electroceuticals can provide disease‐altering treatments. In this review, we provide a brief overview of several of the most thoroughly researched pathogenic hypotheses for Alzheimer's disease (AD) and assess their clinical impact to‐date. We focus specifically on recent research into the role of the locus coeruleus norepinephrine (LC‐NE) system, in both AD pathogenesis and symptom exacerbation, as well as the potential to use advanced neural stimulation techniques as a novel therapeutic option in the earliest stages of neuropathology.
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影响因子：
4.3
作者：
Bonaz B;Bazin T;Pellissier S
通讯作者：
Pellissier S
影响因子：
82.9
作者：
Alonso, AD;GrundkeIqbal, I;Iqbal, K
通讯作者：
Iqbal, K
影响因子：
2.9
作者：
Aston-Jones G;Waterhouse B
通讯作者：
Waterhouse B
影响因子：
25
作者：
Anagnostaras, SG;Murphy, GG;Silva, AJ
通讯作者：
Silva, AJ
DOI：
10.1016/j.jalz.2011.03.008
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Albert MS;DeKosky ST;Dickson D;Dubois B;Feldman HH;Fox NC;Gamst A;Holtzman DM;Jagust WJ;Petersen RC;Snyder PJ;Carrillo MC;Thies B;Phelps CH
通讯作者：
Phelps CH