Aberrant insulin signaling in Alzheimer's disease: current knowledge.
Aberrant insulin signaling in Alzheimer's disease: current knowledge.
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DOI：
10.3389/fnins.2015.00204
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发表时间：
2015
影响因子：
4.3
通讯作者：
Cassano T
中科院分区：
文献类型：
--
作者：
Bedse G;Di Domenico F;Serviddio G;Cassano T
阿尔茨海默病（AD）是影响老年人的痴呆症的最常见形式。AD是一种多方面的病理学，其特征在于细胞外神经炎性斑块、细胞内神经纤维缠结（NFT）的积累和主要在皮质和海马中的神经元损失。AD的病因学似乎与许多尚未完全阐明的机制有关。长期以来，人们认为胰岛素信号转导仅具有外周作用，但现在广泛认为胰岛素在脑内具有神经调节作用。胰岛素信号传导涉及许多脑功能，包括AD中受损的认知和记忆。最近的研究表明，AD可能与脑胰岛素抵抗有关，与健康个体相比，糖尿病患者患AD的风险增加。事实上，胰岛素抵抗、炎症增加和代谢受损是AD和糖尿病的关键病理特征。然而，糖尿病患者发生AD的确切机制尚不完全清楚。在这篇综述中，我们将讨论异常脑胰岛素信号在AD中所起的作用。详细地说，我们将集中于胰岛素信号在神经炎斑块和细胞内NFT沉积中的作用。考虑到胰岛素减轻β-淀粉样蛋白沉积和tau的磷酸化，恢复脑胰岛素信号传导的药理学策略，例如胰岛素的鼻内递送，在AD治疗中可能具有显著的治疗潜力。
Alzheimer's disease (AD) is the most common form of dementia affecting elderly people. AD is a multifaceted pathology characterized by accumulation of extracellular neuritic plaques, intracellular neurofibrillary tangles (NFTs) and neuronal loss mainly in the cortex and hippocampus. AD etiology appears to be linked to a multitude of mechanisms that have not been yet completely elucidated. For long time, it was considered that insulin signaling has only peripheral actions but now it is widely accepted that insulin has neuromodulatory actions in the brain. Insulin signaling is involved in numerous brain functions including cognition and memory that are impaired in AD. Recent studies suggest that AD may be linked to brain insulin resistance and patients with diabetes have an increased risk of developing AD compared to healthy individuals. Indeed insulin resistance, increased inflammation and impaired metabolism are key pathological features of both AD and diabetes. However, the precise mechanisms involved in the development of AD in patients with diabetes are not yet fully understood. In this review we will discuss the role played by aberrant brain insulin signaling in AD. In detail, we will focus on the role of insulin signaling in the deposition of neuritic plaques and intracellular NFTs. Considering that insulin mitigates beta-amyloid deposition and phosphorylation of tau, pharmacological strategies restoring brain insulin signaling, such as intranasal delivery of insulin, could have significant therapeutic potential in AD treatment.
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影响因子：
3.7
作者：
Benedict, C;Hallschmid, M;Kern, W
通讯作者：
Kern, W
影响因子：
--
作者：
Craft, Suzanne;Baker, Laura D.;Montine, Thomas J.;Minoshima, Satoshi;Watson, G. Stennis;Claxton, Amy;Arbuckle, Matthew;Callaghan, Maureen;Tsai, Elaine;Plymate, Stephen R.;Green, Pattie S.;Leverenz, James;Cross, Donna;Gerton, Brooke
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Gerton, Brooke
影响因子：
64.8
作者：
BOLOTINA, VM;NAJIBI, S;COHEN, RA
通讯作者：
COHEN, RA
影响因子：
13.5
作者：
Banks, William A.;Owen, Joshua B.;Erickson, Michelle A.
通讯作者：
Erickson, Michelle A.
影响因子：
4
作者：
Claxton, Amy;Baker, Laura D.;Craft, Suzanne
通讯作者：
Craft, Suzanne