背景:自噬是一种溶酶体依赖性降解途径,可响应多种细胞应激维持细胞稳态。基于动物模型的累积报告表明,这种分解代谢程序在许多人类病理生理条件下的重要性。包括糖尿病,神经退行性疾病,老化,和癌症。因此,自噬作为一种新的治疗靶点,对人类疾病具有广泛的有益作用。这里,我们回顾了我们对自噬知识的最新进展,以及开发自噬调节剂的努力。涵盖的领域:回顾了相关专利(2012-2015年发布)和声称自噬药理调节的研究文献。此外,讨论了它们的分子机制和潜在的治疗效用。专家观点:考虑到自噬诱导的分子机制,靶向自噬特异性蛋白对于设计特异性治疗多种自噬相关疾病的治疗干预措施非常重要.这篇综述中描述的许多专利和研究文献都显示了相关自噬调节剂在癌症或神经变性治疗中的有希望的应用。其中一些已经被考虑用于临床评估。然而,大多数专利都声称自噬的调节剂,但有关其作用机制的信息很少。为了设计高效的疗法,进一步的工作,例如开发特异性靶向自噬特异性机制的化合物,是必需的。
BACKGROUND: Autophagy is a lysosome-dependent degradation pathway that maintains cellular homeostasis in response to a variety of cellular stresses. Accumulating reports based on animal models have indicated the importance of this catabolic program in many human pathophysiological conditions, including diabetes, neurodegenerative diseases, aging, and cancers. Therefore, autophagy has been highlighted as a novel therapeutic target with a wide range of beneficial effects on human diseases. Here, we
review the recent advances of our knowledge toward autophagy, as well as the efforts for developing autophagy modulators. Areas covered: The relevant patents (published at 2012-2015) and the research literature claiming the pharmacological modulation of autophagy are reviewed. Also, their molecular mechanisms and potential therapeutic utilities are discussed. Expert opinion: Considering the molecular machinery involved in autophagy induction, the targeting of autophagy-specific protein is very important to design the therapeutic interventions for specifically treating a variety of autophagy-associated disorders. Many patents and the research literature described in this
review have shown promising applications of the relevant autophagy modulators for cancer or neurodegeneration treatments, a few of which are already being considered for clinical evaluation. However, most patents have claimed the modulators of autophagy with little information regarding their mechanisms of action. To design highly potent therapeutics, further work, such as developing compounds that specifically target the autophagy-specific machinery, are required.