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靶向自噬的药物制剂及其临床应用

Pharmaceutical Agents for Targeting Autophagy and Their Applications in Clinics.

作者信息

Kench Ulash, Sologova Susanna, Smolyarchuk Elena, Prassolov Vladimir, Spirin Pavel

机构信息

Department of Cancer Cell Biology, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova 32, 119991 Moscow, Russia.

Department of Pharmacology, Sechenov University, 119019 Moscow, Russia.

出版信息

Pharmaceuticals (Basel). 2024 Oct 11;17(10):1355. doi: 10.3390/ph17101355.

Abstract

Autophagy is the process by which damaged regions of the cytoplasm and intracellular pathogens are degraded. This mechanism often serves an adaptive role in cells, enhancing their survival. It plays a direct or indirect role in the development of various pathological conditions within the body. This phenomenon is common in various malignant diseases, where autophagy is associated with the resistance of transformed cells to chemotherapy. Conversely, abnormal activation of autophagy can trigger cell death, a process often seen in neurodegenerative conditions. Given that dysregulation of autophagy is associated with the progression of numerous pathological conditions, this is of significant interest to the developers of drugs that can effectively modulate autophagy for both basic research and clinical applications. Here, we provide a brief description of the mechanism of macroautophagy, the most prevalent form of autophagy identified in humans. We also discuss the clinical potential of drugs that can modulate autophagy, highlighting their use in combating diseases associated with direct or indirect dysregulation of this essential process.

摘要

自噬是细胞质受损区域和细胞内病原体被降解的过程。这种机制通常在细胞中发挥适应性作用,增强细胞的生存能力。它在身体内各种病理状况的发展中起直接或间接作用。这种现象在各种恶性疾病中很常见,其中自噬与转化细胞对化疗的抗性有关。相反,自噬的异常激活可引发细胞死亡,这一过程常见于神经退行性疾病。鉴于自噬失调与众多病理状况的进展相关,这对于能够有效调节自噬以用于基础研究和临床应用的药物开发者来说具有重大意义。在此,我们简要描述巨自噬的机制,巨自噬是在人类中发现的最普遍的自噬形式。我们还讨论了能够调节自噬的药物的临床潜力,强调了它们在对抗与这一重要过程的直接或间接失调相关疾病中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9457/11510022/d015bdf83206/pharmaceuticals-17-01355-g001.jpg

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