Department of Biosciences and Bioengineering, Indian Institute of Technology, Guwahati, Assam 781039, India.
CNS Neurol Disord Drug Targets. 2018;17(8):571-589. doi: 10.2174/1871527317666180627122448.
BACKGROUND & OBJECTIVE: Over the last two decades, Alzheimer disease (AD) associated research has accomplished an overwhelming momentum, as it is one of the major current healthcare issues in the developed world. AD is characterized by the presence of Aβ mediated extracellular amyloid fibrils and tau-mediated intracellular neurofibrillar tangles and reports have highlighted their subsequent effects on neuronal synaptic activity, antioxidant response and recently explored mitochondrial dysfunction. Additionally, recent reports have demonstrated the mitochondrial dysfunction and associated physiological as well as cellular alterations triggered by fibrillar structures inside the brain tissue. Accumulated evidence indicated that mitochondrial dysfunction also plays a detrimental role in AD pathogenesis and reduction in mitochondrial dysfunction may provide an additional beneficial effect in AD patients. Currently available drugs are ineffective in disease progression and more symptomatic while mechanism oriented drug explorations have been intensively investigated. Therefore, search for effective therapeutic approaches in Alzheimer disease has directed the ongoing research more towards specific biomarker selection, physicochemical properties of drugs and its subsequent interaction with target molecules.
In present review, we have comprised an overview of the therapeutic advancement in Alzheimer disease with a prevalent hypothesis and current ongoing putative therapeutic approaches to provide recent insights in AD pathogenesis.
在过去的二十年中，阿尔茨海默病（AD）相关研究取得了巨大的进展，因为它是发达国家当前主要的医疗保健问题之一。AD 的特征是存在 Aβ介导的细胞外淀粉样纤维和 tau 介导的细胞内神经原纤维缠结，有报道强调了它们对神经元突触活动、抗氧化反应以及最近探索的线粒体功能障碍的后续影响。此外，最近的报告表明，脑组织内纤维状结构会引发线粒体功能障碍以及相关的生理和细胞改变。越来越多的证据表明，线粒体功能障碍在 AD 发病机制中也起着有害作用，减少线粒体功能障碍可能会为 AD 患者提供额外的有益效果。目前可用的药物对疾病进展无效，更多的是对症治疗，而针对机制的药物探索已得到深入研究。因此，针对阿尔茨海默病的有效治疗方法的研究方向更多地指向了特定的生物标志物选择、药物的物理化学性质及其与靶分子的后续相互作用。
在本次综述中，我们对阿尔茨海默病的治疗进展进行了概述，提出了一个流行的假说和当前正在进行的潜在治疗方法，为 AD 发病机制提供了最新的见解。
