Targeting autophagy and beyond: Deconvoluting the complexity of Beclin-1 from biological function to cancer therapy

Ye, Jing; Zhang, Jin; Zhu, Yanghui; Wang, Lian; Jiang, Xian; Liu, Bo; He, Gu

doi:10.1016/j.apsb.2023.08.008

Cited by 7 publications

(4 citation statements)

References 295 publications

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“…On the other hand, impaired autophagy can also lead to the accumulation of ubiquitinated proteins and the damage of organelles and even accelerate the process of apoptosis or necrosis . Beclin 1 is considered as a common index for detecting autophagy . In the brains of AD models, Beclin 1 expression is significantly reduced, and autophagosomes are formed in neurons, leading to a large number of lysosomal ruptures, which accelerates the abnormal accumulation of Aβ and intensifies neuronal cell degeneration .…”

Section: Discussionmentioning

confidence: 99%

“…46 Beclin 1 is considered as a common index for detecting autophagy. 47 In the brains of AD models, Beclin 1 expression is significantly reduced, and autophagosomes are formed in neurons, leading to a large number of lysosomal ruptures, which accelerates the abnormal accumulation of Aβ and intensifies neuronal cell degeneration. 48 LC3 is another specific gene for mammalian autophagy.…”

Section: Journal Ofmentioning

confidence: 99%

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Pongamol Alleviates Neuroinflammation and Promotes Autophagy in Alzheimer’s Disease by Regulating the Akt/mTOR Signaling Pathway

Hu,

Wu,

et al. 2024

J. Agric. Food Chem.

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Alzheimer's disease (AD), one of the neurodegenerative disorders, is highly correlated with the abnormal hyperphosphorylation of Tau and aggregation of β-amyloid (Aβ). Oxidative stress, neuroinflammation, and abnormal autophagy are key drivers of AD and how they contribute to neuropathology remains largely unknown. The flavonoid compound pongamol is reported to possess a variety of pharmacological activities, such as antioxidant, antibacterial, and anti-inflammatory. This study investigated the neuroprotective effect and its mechanisms of pongamol in lipopolysaccharide (LPS)-induced BV2 cells, d-galactose/ sodium nitrite/aluminum chloride (D-gal/NaNO 2 /AlCl 3 )-induced AD mice, and Caenorhabditis elegans models. Our research revealed that pongamol reduced the release of inflammatory factors IL-1β, TNF-α, COX-2, and iNOS in LPS-induced BV2 cells. Pongamol also protected neurons and significantly restored memory function, inhibited Tau phosphorylation, downregulated Aβ aggregation, and increased oxidoreductase activity in the hippocampus of AD mice. In addition, pongamol reversed the nuclear transfer of NF-κB and increased the levels of Beclin 1 and LC3 II/LC3 I. Most importantly, the anti-inflammatory and promoter autophagy effects of pongamol may be related to the regulation of the Akt/mTOR signaling pathway. In summary, these results showed that pongamol has a potential neuroprotective effect, which greatly enriched the research on the pharmacological activity of pongamol for improving AD.

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Section: Discussionmentioning

confidence: 99%

Section: Journal Ofmentioning

confidence: 99%

Pongamol Alleviates Neuroinflammation and Promotes Autophagy in Alzheimer’s Disease by Regulating the Akt/mTOR Signaling Pathway

Hu,

Wu,

et al. 2024

J. Agric. Food Chem.

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“…Upon the reduction of the ATP/AMP ratio, the activation of AMPK recruits ULK1 and BECN1, resulting in the stimulation autophagy signaling pathway ( Bujak et al, 2015 ; Klionsky et al, 2021 ). BECN1 is a scaffolding protein that facilitates the formation of class III PI3K complex ( Ye et al, 2023 ). In the class III PI3K complex, the direct interaction of ATG14L and UVRAG with BECN1 leads to the activation of VPS34, and VPS15 ( Ye et al, 2023 ).…”

Section: Autophagy Mechanisms and Molecular Machinerymentioning

confidence: 99%

“…BECN1 is a scaffolding protein that facilitates the formation of class III PI3K complex ( Ye et al, 2023 ). In the class III PI3K complex, the direct interaction of ATG14L and UVRAG with BECN1 leads to the activation of VPS34, and VPS15 ( Ye et al, 2023 ). It is thought that VPS34 is a catalytic PI3K and participates in the formation of PI3-phosphate (PI3P).…”

Section: Autophagy Mechanisms and Molecular Machinerymentioning

confidence: 99%

Role of autophagy in angiogenic potential of vascular pericytes

Milani,

Rezabakhsh,

Karimipour

et al. 2024

Front. Cell Dev. Biol.

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The vasculature system is composed of a multiplicity of juxtaposed cells to generate a functional biological barrier between the blood and tissues. On the luminal surface of blood vessels, endothelial cells (ECs) are in close contact with circulating cells while supporting basal lamina and pericytes wrap the abluminal surface. Thus, the reciprocal interaction of pericytes with ECs is a vital element in the physiological activity of the vascular system. Several reports have indicated that the occurrence of pericyte dysfunction under ischemic and degenerative conditions results in varied micro and macro-vascular complications. Emerging evidence points to the fact that autophagy, a conserved self-digestive cell machinery, can regulate the activity of several cells like pericytes in response to various stresses and pathological conditions. Here, we aim to highlight the role of autophagic response in pericyte activity and angiogenesis potential following different pathological conditions.

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A promising future of metal‐N‐heterocyclic carbene complexes in medicinal chemistry: The emerging bioorganometallic antitumor agents

Zhao,

Han,

Peng

et al. 2024

Medicinal Research Reviews

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Metal complexes based on N‐heterocyclic carbene (NHC) ligands have emerged as promising broad‐spectrum antitumor agents in bioorganometallic medicinal chemistry. In recent decades, studies on cytotoxic metal–NHC complexes have yielded numerous compounds exhibiting superior cytotoxicity compared to cisplatin. Although the molecular mechanisms of these anticancer complexes are not fully understood, some potential targets and modes of action have been identified. However, a comprehensive review of their biological mechanisms is currently absent. In general, apoptosis caused by metal–NHCs is common in tumor cells. They can cause a series of changes after entering cells, such as mitochondrial membrane potential (MMP) variation, reactive oxygen species (ROS) generation, cytochrome c (cyt c) release, endoplasmic reticulum (ER) stress, lysosome damage, and caspase activation, ultimately leading to apoptosis. Therefore, a detailed understanding of the influence of metal–NHCs on cancer cell apoptosis is crucial. In this review, we provide a comprehensive summary of recent advances in metal–NHC complexes that trigger apoptotic cell death via different apoptosis‐related targets or signaling pathways, including B‐cell lymphoma 2 (Bcl‐2 family), p53, cyt c, ER stress, lysosome damage, thioredoxin reductase (TrxR) inhibition, and so forth. We also discuss the challenges, limitations, and future directions of metal–NHC complexes to elucidate their emerging application in medicinal chemistry.

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Targeting autophagy and beyond: Deconvoluting the complexity of Beclin-1 from biological function to cancer therapy

Cited by 7 publications

References 295 publications

Pongamol Alleviates Neuroinflammation and Promotes Autophagy in Alzheimer’s Disease by Regulating the Akt/mTOR Signaling Pathway

Pongamol Alleviates Neuroinflammation and Promotes Autophagy in Alzheimer’s Disease by Regulating the Akt/mTOR Signaling Pathway

Role of autophagy in angiogenic potential of vascular pericytes

A promising future of metal‐N‐heterocyclic carbene complexes in medicinal chemistry: The emerging bioorganometallic antitumor agents

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