Therapeutic Implications of Autophagy Inducers in Immunological Disorders, Infection, and Cancer

Byun, Sun‐Sig; Lee, Eunjung; Lee, Ki Won

doi:10.3390/ijms18091959

Cited by 53 publications

(35 citation statements)

References 193 publications

(166 reference statements)

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“…The term "autophagic flux" reflects the completion of the entire dynamic process of autophagosome formation and then fusion with lysosomes, subsequent degradation of cargo, and release of degradation products [11]. Autophagy disturbances are frequently caused by these mechanisms: inhibition of autophagy initiation, interruption of autophagosome-lysosome fusion, and damage to lysosomal function [12]. Moreover, autophagy dysfunction has been widely reported to be closely related to cell senescence and apoptosis in the progression of several diseases, particularly degenerative diseases such as osteoarthritis [13], IDD [14], neurodegenerative disorders [15], and age-related macular degeneration [16].…”

Section: Introductionmentioning

confidence: 99%

Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration

Kang

Xiang

Zhan

et al. 2019

Oxidative Medicine and Cellular Longevity

107

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Oxidative stress-induced mitochondrial dysfunction and nucleus pulposus (NP) cell apoptosis play crucial roles in the development of intervertebral disc degeneration (IDD). Increasing studies have shown that interventions targeting impaired autophagic flux can maintain cellular homeostasis by relieving oxidative damage. Here, we investigated the effect of curcumin (CUR), a known autophagy activator, on IDD in vitro and in vivo. CUR suppressed tert-butyl hydroperoxide- (TBHP-) induced oxidative stress and mitochondrial dysfunction and thereby inhibited human NP cell apoptosis, senescence, and ECM degradation. CUR treatment induced autophagy and enhanced autophagic flux in an AMPK/mTOR/ULK1-dependent manner. Notably, CUR alleviated TBHP-induced interruption of autophagosome-lysosome fusion and impairment of lysosomal function and thus contributed to the restoration of blocked autophagic clearance. These protective effects of CUR in TBHP-stimulated human NP cells resembled the effects produced by the autophagy inducer rapamycin, but the effects were partially eliminated by 3-methyladenine- and compound C-mediated inhibition of autophagy initiation or chloroquine-mediated obstruction of autophagic flux. Lastly, CUR also exerted a protective effect against puncture-induced IDD progression in vivo. Our results showed that suppression of excessive ROS production and mitochondrial dysfunction through enhancement of autophagy coupled with restoration of autophagic flux ameliorated TBHP-induced human NP cell apoptosis, senescence, and ECM degradation. Thus, maintenance of the proper functioning of autophagy represents a promising therapeutic strategy for IDD, and CUR might serve as an effective therapeutic agent for IDD.

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Section: Introductionmentioning

confidence: 99%

Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration

Kang

Xiang

Zhan

et al. 2019

Oxidative Medicine and Cellular Longevity

107

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show abstract

“…This process is essential to maintain the metabolism essential for cell survival under stress situations. However, dysfunction of autophagy is involved in multiple diseases, including infectious diseases, cancers and TBI (Lipinski et al, 2015 ; Byun et al, 2017 ). Therefore, clarifying the molecular mechanisms of this degradation process may contribute to develop novel treatment protocols for therapeutic purposes.…”

Section: Introductionmentioning

confidence: 99%

Autophagy in Traumatic Brain Injury: A New Target for Therapeutic Intervention

Zhang

Wang

2018

Front. Mol. Neurosci.

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Traumatic brain injury (TBI) is one of the most devastating forms of brain injury. Many pathological mechanisms such as oxidative stress, apoptosis and inflammation all contribute to the secondary brain damage and poor outcomes of TBI. Current therapies are often ineffective and poorly tolerated, which drive the explore of new therapeutic targets for TBI. Autophagy is a highly conserved intracellular mechanism during evolution. It plays an important role in elimination abnormal intracellular proteins or organelles to maintain cell stability. Besides, autophagy has been researched in various models including TBI. Previous studies have deciphered that regulation of autophagy by different molecules and pathways could exhibit anti-oxidative stress, anti-apoptosis and anti-inflammation effects in TBI. Hence, autophagy is a promising target for further therapeutic development in TBI. The present review provides an overview of current knowledge about the mechanism of autophagy, the frequently used methods to monitor autophagy, the functions of autophagy in TBI as well as its potential molecular mechanisms based on the pharmacological regulation of autophagy.

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“…Активаторами аутофагии являются следующие вещества: BRD5631, сперминидин, трехалоза, а также витамин Д3 и другие. Считается, что их действие сопряжено с активацией иммунной системы за счет изменения состояния AKT/mTOR сигнального пути [18]. Byun S. и соавторы также подробно описали влияние рапамицина и его аналогов, метформина, обатоклакса (GX15-070), линзинина, а также мапротилина и флуоксетина в гибели трансформированных клеток за счет активации аутофагии.…”

Section: молекулярные механизмы вовлеченные в развитие аутофагииunclassified

The role of autophagy in the thyroid tumors development, connection with the AKT/m-TOR signaling pathway activation

et al. 2020

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Autophagy is an important intracellular process that supports cell death and survival. Oncogenesis is associated with a change in the AKT/mTOR signaling pathway status. At the same time, the existence of protective autophagy, as one of the mechanisms of disease progression and the formation of resistance to treatment, has been proven. The review describes the significant mechanisms of the autophagy development, its association with AKT/mTOR signaling pathway. A molecule mTOR in TORC1 complex is associated with the oncogenesis, it provides the proliferation of transformed cells, apoptosis inhibition, and to the development of autophagy. The participation of this phenomenon at all stages of carcinogenesis, influencing on the main signal kinases: AKT, mTOR, is noted. It is shown that in most cases this mechanism is responsible for the progression of the disease and the development of resistance to treatment. The development of thyroid cancer associated with the BRAF mutation and with the activation of the RET oncoprotein, as well as with the formation of radio-resistant forms of the disease is associated with molecular peculiarities of autophagy. Given the inconsistency of this phenomenon regarding their influence on the processes of oncogenesis, its role in the development of thyroid cancer is still unknown.

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Therapeutic Implications of Autophagy Inducers in Immunological Disorders, Infection, and Cancer

Cited by 53 publications

References 193 publications

Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration

Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration

Autophagy in Traumatic Brain Injury: A New Target for Therapeutic Intervention

The role of autophagy in the thyroid tumors development, connection with the AKT/m-TOR signaling pathway activation

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