Department of Pharmaceutical Sciences, University of Catania, 95125, Catania, Italy.
Eur J Pharmacol. 2010 Jan 10;626(1):64-71. doi: 10.1016/j.ejphar.2009.10.022. Epub 2009 Oct 18.
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-adrenal (HPA) 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 beta1 (TGF-beta1) 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.
抑郁症是最常见和最具威胁生命的精神疾病之一，而阿尔茨海默病则是一种神经退行性疾病，影响着全球超过 3700 万人。最近的证据表明，抑郁症和阿尔茨海默病之间存在很强的关系。一生中患有重度抑郁症被认为是日后发生阿尔茨海默病的一个风险因素。抑郁症状的存在会影响轻度认知障碍向阿尔茨海默病的转化。神经原纤维缠结和神经纤维缠结，阿尔茨海默病大脑的两个主要特征，在伴有抑郁的阿尔茨海默病患者的大脑中比不伴有抑郁的阿尔茨海默病患者更为明显。另一方面，在有抑郁病史的患者的不同大脑区域也观察到了神经退行性现象。最近的证据表明，在重度抑郁症发病机制中起作用的分子机制和级联反应，如慢性炎症和下丘脑-垂体-肾上腺 (HPA) 轴的过度激活，也与阿尔茨海默病的发病机制有关。特别是，在抑郁症和阿尔茨海默病中都观察到某些神经营养因子（如转化生长因子β 1 (TGF-β1) 和脑源性神经营养因子 (BDNF)）的信号转导存在特定缺陷。在本综述中，我们将检查抑郁症和阿尔茨海默病之间共同分子途径的证据，并将这些途径作为治疗这两种疾病的新的药理学靶点进行讨论。
