Cenini Giovanna, Voos Wolfgang
Institut für Biochemie und Molekularbiologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
Front Pharmacol. 2019 Aug 23;10:902. doi: 10.3389/fphar.2019.00902. eCollection 2019.
Alzheimer disease (AD) is a progressive and deleterious neurodegenerative disorder that affects mostly the elderly population. At the moment, no effective treatments are available in the market, making the whole situation a compelling challenge for societies worldwide. Recently, novel mechanisms have been proposed to explain the etiology of this disease leading to the new concept that AD is a multifactor pathology. Among others, the function of mitochondria has been considered as one of the intracellular processes severely compromised in AD since the early stages and likely represents a common feature of many neurodegenerative diseases. Many mitochondrial parameters decline already during the aging, reaching an extensive functional failure concomitant with the onset of neurodegenerative conditions, although the exact timeline of these events is still unclear. Thereby, it is not surprising that mitochondria have been already considered as therapeutic targets in neurodegenerative diseases including AD. Together with an overview of the role of mitochondrial dysfunction, this review examines the pros and cons of the tested therapeutic approaches targeting mitochondria in the context of AD. Since mitochondrial therapies in AD have shown different degrees of progress, it is imperative to perform a detailed analysis of the significance of mitochondrial deterioration in AD and of a pharmacological treatment at this level. This step would be very important for the field, as an effective drug treatment in AD is still missing and new therapeutic concepts are urgently needed.
阿尔茨海默病(AD)是一种进行性且有害的神经退行性疾病,主要影响老年人群。目前,市场上尚无有效的治疗方法,这使得全球社会面临着严峻挑战。最近,人们提出了新的机制来解释这种疾病的病因,从而产生了AD是一种多因素病理学的新概念。其中,线粒体功能自早期阶段起就被认为是AD中严重受损的细胞内过程之一,并且可能是许多神经退行性疾病的共同特征。许多线粒体参数在衰老过程中就已下降,随着神经退行性疾病的发作,会出现广泛的功能衰竭,尽管这些事件的确切时间线仍不清楚。因此,线粒体已被视为包括AD在内的神经退行性疾病的治疗靶点也就不足为奇了。除了概述线粒体功能障碍的作用外,本综述还探讨了在AD背景下针对线粒体的已测试治疗方法的利弊。由于AD中线粒体疗法已显示出不同程度的进展,因此有必要详细分析AD中线粒体退化的意义以及在此层面上进行药物治疗的情况。这一步骤对该领域非常重要,因为AD仍缺乏有效的药物治疗,迫切需要新的治疗概念。