溶酶体贮积病:诱导自噬的天然产物

IF 0.3 Q4 PHARMACOLOGY & PHARMACY Current Drug Therapy Pub Date : 2023-09-15 DOI:10.2174/1574885519666230915103100
Chandani Chandrana, Tahib Habshi, Arun Soni, Sanjeev Acharya
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引用次数: 0

摘要

背景:近几十年来,自噬和溶酶体功能之间的联系已经得到了很好的认识;有缺陷的自噬和溶酶体功能导致各种疾病,特别是溶酶mal Storage disorders (lsd)。多种机制通路的故障影响lsd的作用。在这种情况下采用了不同的方法,但一种新的方法可以通过诱导自噬途径来解决问题,这有助于维持适当的自噬和溶酶体降解功能。方法:自噬诱导剂对转录因子EB (TFEB)的激活作用及其机制;mTOR复合物抑制可依赖或独立地修复整个机制的功能缺陷。寻找潜在的自噬诱导剂仍在进行中,但靶向TFEB和mTOR可能会重新定义LSD治疗。实验中发现的TFEB调节剂可以增强自噬通量,促进溶酶体功能,增加溶酶体的生物发生,是治疗溶酶体贮积症等由ALP功能障碍引起的疾病的一种很有前景的技术。结果:抑制MTORC1可使TFEB转运至细胞核,参与自噬体和溶酶体形成的多个基因转录,说明MTORC1对Pompe病、baton病、Fabry病等溶酶体贮积性疾病有积极作用,调节自噬可减轻上述情况。结论:本文综述了细胞自噬和溶酶体的结合,它们的功能障碍导致各种溶酶体疾病。还讨论了几种可能作为治疗选择的天然产品。
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Lysosomal storage diseases: Natural products inducing autophagy
Background: The link between autophagy and lysosomal function has been well-recognised in recent dec-ades; defective autophagy and lysosomal function lead to various disorders, notably Lysoso-mal Storage Disorders (LSDs). The malfunction of multiple mechanistic pathways influences the contribution of LSDs. Different ways are employed in such situations, but one novel ap-proach could resolve the problem by inducing the autophagic pathway, which aids in main-taining proper autophagy and lysosomal degradation function. Method: Autophagic Inducer functions on the activation of Transcriptional factor EB (TFEB) and its mechanism; mTOR Complex Inhibition dependently or independently may repair the mal-function of the entire mechanism. Finding a potential autophagic inducer is still a work in progress, but targeting TFEB and mTOR could redefine LSD treatment. The development of experimentally available TFEB modulators could enhance autophagic flux promote lysosomal function and increase lysosomal biogenesis and can be a promising technique for treating ill-nesses caused by ALP dysfunction, such as lysosomal storage disorder. Result: MTORC1 suppression causes TFEB to be transported to the nucleus and transcription of mul-tiple genes involved in the formation of autophagosomes and lysosomes, indicating that MTORC1 has positive effects in treating lysosomal storage diseases such as Pompe disease, Batton disease, Fabry disease, etc. thus modulating autophagy attenuates the above condi-tion. Conclusion: This review comprises autophagy and lysosome association, and their malfunction leads to various lysosomal diseases. Several natural products are also discussed, which can be possible treatment options.
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来源期刊
Current Drug Therapy
Current Drug Therapy PHARMACOLOGY & PHARMACY-
CiteScore
1.30
自引率
0.00%
发文量
50
期刊介绍: Current Drug Therapy publishes frontier reviews of high quality on all the latest advances in drug therapy covering: new and existing drugs, therapies and medical devices. The journal is essential reading for all researchers and clinicians involved in drug therapy.
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