Depression and Alzheimer's disease: Neurobiological links and common pharmacological targets
Depression and Alzheimer's disease: Neurobiological links and common pharmacological targets
复制标题
DOI：
10.1016/j.ejphar.2009.10.022
复制
发表时间：
2010-01-10
影响因子：
5
通讯作者：
Drago, Filippo
中科院分区：
文献类型：
--
作者：
Caraci, Filippo;Copani, Agata;Drago, Filippo
抑郁症是最普遍和最威胁生命的精神疾病之一，而阿尔茨海默病是一种神经退行性疾病，全球有3700万人受到影响。最近的证据表明，抑郁症和阿尔茨海默病之间有很强的联系。终生抑郁症史被认为是阿尔茨海默病未来发展的危险因素。抑郁症状的出现会影响轻度认知障碍转变为阿尔茨海默病。阿尔茨海默病大脑的两大特征--神经性斑块和神经原纤维缠结，在患有抑郁症的阿尔茨海默病患者的大脑中比没有抑郁症的阿尔茨海默病患者的大脑中更加明显。另一方面，在有抑郁症病史的患者的不同大脑区域也观察到了神经退化现象。最近的证据表明，抑郁症发病的分子机制和级联反应，如慢性炎症和下丘脑-垂体-肾上腺皮质(HIPA)轴的过度激活，也参与了阿尔茨海默病的发病。特别是，在抑郁症和阿尔茨海默病中都观察到了一些神经营养因子如转化生长因子β1和脑源性神经营养因子的信号转导的特异性损伤。在这篇综述中，我们将考察抑郁症和阿尔茨海默病之间常见的分子通路的证据，并讨论这些通路作为治疗严重抑郁症和阿尔茨海默病的新的药理学靶点。(C)2009爱思唯尔B.V.保留所有权利。
Depression is one of the most prevalent and life-threatening forms of mental illnesses, whereas Alzheimer's disease is a neurodegenerative disorder that affects more than 37 million people worldwide. Recent evidence suggests a strong relationship between depression and Alzheimer's disease. A lifetime history of major depression has been considered as a risk factor for later development of Alzheimer's disease. The presence of depressive symptoms can affect the conversion of mild cognitive impairment into Alzheimer's disease. Neuritic plaques and neurofibrillary tangles, the two major hallmarks of Alzheimer's disease brain, are more pronounced in the brains of Alzheimer's disease patients with comorbid depression as compared with Alzheimer's disease patients without depression. On the other hand, neurodegenerative phenomena have been observed in different brain regions of patients with a history of depression. Recent evidence suggests that molecular mechanisms and cascades that underlie the pathogenesis of major depression, such as chronic inflammation and hyperactivation of hypothalamic-pituitary-ad renal (HIPA) axis, are also involved in the pathogenesis of Alzheimer's disease. In particular, a specific impairment in the signaling of some neurotrophins such as transforming-growth-factor beta 1 (TGF-beta 1) and brain-derived neurotrophic factor (BDNF) has been observed both in depression and Alzheimer's disease. In the present review we will examine the evidence on the common molecular pathways between depression and Alzheimer's disease and we will discuss these pathways as new pharmacological targets for the treatment of both major depression and Alzheimer's disease. (C) 2009 Elsevier B.V. All rights reserved.