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首页> 外文期刊>Current neuropharmacology >Consequences of Aberrant Insulin Regulation in the Brain: Can Treating Diabetes be Effective for Alzheimer’s Disease
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Consequences of Aberrant Insulin Regulation in the Brain: Can Treating Diabetes be Effective for Alzheimer’s Disease

机译：大脑中异常胰岛素调节的后果：可以治疗糖尿病对阿尔茨海默氏病有效

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There is an urgent need for new ways to treat Alzheimer’s disease (AD), the most common cause of dementia in the elderly. Current therapies are modestly effective at treating the symptoms, and do not significantly alter the course of the disease. Over the years, a range of epidemiological and experimental studies have demonstrated interactions between diabetes mellitus and AD. As both diseases are leading causes of morbidity and mortality in the elderly and are frequent co-morbid conditions, it has raised the possibility that treating diabetes might be effective in slowing AD. This is currently being attempted with drugs such as the insulin sensitizer rosiglitazone. These two diseases share many clinical and biochemical features, such as elevated oxidative stress, vascular dysfunction, amyloidogenesis and impaired glucose metabolism suggesting common pathogenic mechanisms. The main thrust of this review will be to explore the evidence from a pathological point of view to determine whether diabetes can cause or exacerbate AD. This was supported by a number of animal models of AD that have been shown to have enhanced pathology when diabetic conditions were induced. The one drawback in linking diabetes and insulin to AD has been the postmortem studies of diabetic brains demonstrating that AD pathology was not increased; in fact decreased pathology has often been reported. In addition, diabetes induces its own distinct features of neuropathology different from AD. There are common pathological features to be considered including vascular abnormalities, a major feature arising from diabetes; there is increasing evidence that vascular abnormalities can contribute to AD. The most important common mechanism between insulin-resistant (type II) diabetes and AD could be impaired insulin signaling; a form of toxic amyloid can damage neuronal insulin receptors and affect insulin signaling and cell survival. It has even been suggested that AD could be considered as “type 3 diabetes” since insulin can be produced in brain. Another common feature of diabetes and AD are increased advanced glycation endproduct-modified proteins are found in diabetes and in the AD brain; the receptor for advanced glycation endproducts plays a prominent role in both diseases. In addition, a major role for insulin degrading enzyme in the degradation of Aβ peptide has been identified. Although clinical trials of certain types of diabetic medications for treatment of AD have been conducted, further understanding the common pathological processes of diabetes and AD are needed to determine whether these diseases share common therapeutic targets.
机译：迫切需要新的方法来治疗老年痴呆症最常见的病因-阿尔茨海默氏病（AD）。当前的疗法在治疗症状方面适度有效，并且不会显着改变疾病的进程。多年来，一系列的流行病学和实验研究已经证明了糖尿病与AD之间的相互作用。由于这两种疾病都是老年人发病和死亡的主要原因，并且都是常见的合并病，因此增加了治疗糖尿病可能有效减缓AD的可能性。当前正在尝试使用诸如胰岛素敏化剂罗格列酮的药物。这两种疾病具有许多临床和生化特征，例如氧化应激升高，血管功能障碍，淀粉样蛋白生成和葡萄糖代谢受损，提示常见的致病机制。这篇综述的主要目的是从病理学角度探讨证据，以确定糖尿病是否会引起或加重AD。这被许多AD动物模型所支持，这些动物模型已被证明在诱导糖尿病疾病时具有增强的病理性。糖尿病和胰岛素与AD关联的一个缺点是糖尿病大脑的验尸研究表明AD病理没有增加。实际上，经常有病理减少的报道。另外，糖尿病诱发与AD不同的其自身独特的神经病理学特征。需要考虑的常见病理特征包括血管异常，这是糖尿病引起的主要特征。越来越多的证据表明血管异常可导致AD。胰岛素抵抗性（II型）糖尿病和AD之间最重要的共同机制可能是胰岛素信号传导受损。一种有毒的淀粉样蛋白会损害神经元胰岛素受体并影响胰岛素信号传导和细胞存活。甚至有人认为，AD可以被认为是“ 3型糖尿病”，因为胰岛素可以在大脑中产生。糖尿病和AD的另一个共同特征是，在糖尿病和AD脑中发现晚期糖基化终产物修饰的蛋白质增加。晚期糖基化终产物的受体在两种疾病中都起着重要作用。另外，已经确定了胰岛素降解酶在Aβ肽降解中的主要作用。尽管已经进行了某些类型的糖尿病药物治疗AD的临床试验，但需要进一步了解糖尿病和AD的常见病理过程，以确定这些疾病是否具有相同的治疗靶点。

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