Uddin Md Sahab, Stachowiak Anna, Mamun Abdullah Al, Tzvetkov Nikolay T, Takeda Shinya, Atanasov Atanas G, Bergantin Leandro B, Abdel-Daim Mohamed M, Stankiewicz Adrian M
Department of Pharmacy, Southeast University, Dhaka, Bangladesh.
Department of Experimental Embryology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Magdalenka, Poland.
Front Aging Neurosci. 2018 Jan 30;10:04. doi: 10.3389/fnagi.2018.00004. eCollection 2018.
Alzheimer's disease (AD) is the most common cause of progressive dementia in the elderly. It is characterized by a progressive and irreversible loss of cognitive abilities and formation of senile plaques, composed mainly of amyloid β (Aβ), and neurofibrillary tangles (NFTs), composed of tau protein, in the hippocampus and cortex of afflicted humans. In brains of AD patients the metabolism of Aβ is dysregulated, which leads to the accumulation and aggregation of Aβ. Metabolism of Aβ and tau proteins is crucially influenced by autophagy. Autophagy is a lysosome-dependent, homeostatic process, in which organelles and proteins are degraded and recycled into energy. Thus, dysfunction of autophagy is suggested to lead to the accretion of noxious proteins in the AD brain. In the present review, we describe the process of autophagy and its importance in AD. Additionally, we discuss mechanisms and genes linking autophagy and AD, i.e., the mTOR pathway, neuroinflammation, endocannabinoid system, , and . We also present pharmacological agents acting via modulation of autophagy that may show promise in AD therapy. This review updates our knowledge on autophagy mechanisms proposing novel therapeutic targets for the treatment of AD.
阿尔茨海默病（AD）是老年人进行性痴呆最常见的病因。其特征是认知能力进行性且不可逆丧失，以及在患病个体的海马体和皮质中形成主要由淀粉样β（Aβ）组成的老年斑和由tau蛋白组成的神经原纤维缠结（NFTs）。在AD患者的大脑中，Aβ的代谢失调，导致Aβ的积累和聚集。Aβ和tau蛋白的代谢受到自噬的关键影响。自噬是一种依赖溶酶体的稳态过程，其中细胞器和蛋白质被降解并再循环为能量。因此，自噬功能障碍被认为会导致AD大脑中有害蛋白质的积累。在本综述中，我们描述了自噬过程及其在AD中的重要性。此外，我们讨论了连接自噬和AD的机制和基因，即mTOR途径、神经炎症、内源性大麻素系统等。我们还介绍了通过调节自噬起作用的药物制剂，这些制剂可能在AD治疗中显示出前景。本综述更新了我们对自噬机制的认识，为AD治疗提出了新的治疗靶点。
