Application of Nanomaterials and Related Drug Delivery Systems in Autophagy

Molecules, Год журнала: 2024, Номер 29(15), С. 3513 - 3513

Опубликована: Июль 26, 2024

Autophagy, a lysosomal self-degradation pathway, plays critical role in cellular homeostasis by degrading endogenous damaged organelles and protein aggregates into recyclable biological molecules. Additionally, it detoxifies extracellular toxic substances, including drugs materials, thereby preserving the stability of intracellular environment. The swift progression nanotechnology has led to an increased focus on understanding relationship between nanomaterials autophagy. effects various nano drug delivery systems autophagy their functions have been preliminarily assessed, revealing that modulation levels these agents represents novel response mechanism. Notably, regulation based or for range diseases is currently subject extensive research. Given close association tumors, emerged as highly active area research development innovative tumor therapies. This review synthesizes current application potential functions, suggesting new avenue nanomaterial-based regulation.

Язык: Английский

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The Role of Autophagy in Copper-Induced Apoptosis and Developmental Neurotoxicity in SH-SY5Y Cells

Toxics, Год журнала: 2025, Номер 13(1), С. 63 - 63

Опубликована: Янв. 17, 2025

Copper (Cu) is a global environmental pollutant that poses serious threat to humans and ecosystems. induces developmental neurotoxicity, but the underlying molecular mechanisms are unknown. Neurons nonrenewable, they unable mitigate excessive accumulation of pathological proteins organelles in cells, which can be ameliorated by autophagic degradation. In this study, we established an vitro model Cu2+-exposed (0, 15, 30, 60 120 μM) SH-SY5Y cells explore role autophagy copper-induced neurotoxicity. The results showed copper resulted reduction shortening neural synapses differentiated cultured downregulated Wnt signaling pathway, nuclear translocation β-catenin. Exposure Cu2+ increased autophagosome flux blockage terms sequestosome 1 (p62/SQSTM1) microtubule-associated protein light chain 3B (LC3B) II/LC3BI expressions inhibition phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway. Furthermore, induced apoptosis, characterized Bcl2 X (Bax), caspase 3, Poly (ADP-ribose) polymerase (PARP) decreased expression B-cell lymphoma 2 (Bcl2). Compared with μM exposure group alone, activator rapamycin pretreatment β-catenin translocation, LC3BII/LC3BI p62, as well upregulated 3 PARP. contrast, after inhibitor chloroquine pretreatment, were decreased, levels p62 upregulated, was while Bax, PARP increased. conclusion, study demonstrated associated neurotoxicity via might deepen understanding mechanism exposure.

Язык: Английский

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How does autophagy impact neurological function?

The Neuroscientist, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Autophagies describe a set of processes in which cells degrade their cytoplasmic contents via various routes that terminate with the lysosome. In macroautophagy (the focus this review, henceforth autophagy), contents, including misfolded proteins, protein complexes, dysfunctional organelles, and pathogens, are captured within double membranes called autophagosomes, ultimately fuse lysosomes, after degraded. Autophagy is important maintaining neuronal glial function; consequently, disrupted autophagy associated neurologic diseases. This review provides broad perspective on roles CNS, highlighting recent literature furthers our understanding multifaceted role healthy nervous system.

Язык: Английский

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Small HSPs at the crossroad between protein aggregation, autophagy and unconventional secretion: clinical implications and potential therapeutic opportunities in the context of neurodegenerative diseases

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Май 2, 2025

Neurodegenerative diseases (NDs) such as Alzheimer’s, Parkinson’s and Huntington’s well ataxias fronto-temporal disorders are all characterized by the progressive accumulation of protein aggregates (amyloids) into inclusions bodies. In addition, recent experimental evidence is challenging conventional view disease revealing ability some these disease-relevant proteins to be transferred between cells means extracellular vesicles (EVs), allowing mutant seed oligomers involving both wild type forms protein. Abnormal secretion levels EVs closely related pathogenesis neurodegenerative contribute progression. Numerous studies have proposed therapeutic targets or biomarkers for diseases. this review, we summarize discuss role small heat shock (sHSPs) autophagy in cellular quality control turn-over major aggregation-prone associated disorders. We also highlight advanced research progress on mechanisms regulating unconventional secretion, secretory biogenesis their contribution pathological processes underlining Finally, outline latest roles potential diagnostic significance treatment clinically relevant conditions.

Язык: Английский

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Targeting TRPML3 inhibits proliferation and invasion, and enhances doxorubicin sensitivity by disrupting lysosomal acidification and mitochondrial function in triple-negative breast cancer

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Год журнала: 2025, Номер unknown, С. 119979 - 119979

Опубликована: Май 1, 2025

Язык: Английский

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Promoting Secretion of Pathological Tau Species Using an Induced Proximity Platform That Engages the Autophagy Pathway

ACS Chemical Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Май 9, 2025

Intracellular accumulation of aberrantly phosphorylated aggregated tau protein can contribute to neuronal dysfunction associated with many neurodegenerative diseases. Thus, removing such species is an attractive therapeutic hypothesis for these Targeted degradation (TPD) strategies leveraging the autophagy-lysosome pathway (ALP) are promising approaches decrease aggregates by designating them degradation. Here, we developed a novel heterobifunctional molecule, MRL828, combining pathology-binding ligand and modified guanine moiety based on autophagy-targeting chimaera technology selectively designate proteins clearance via ALP. Surprisingly, MRL828-dependent in intracellular was dependent autophagosome, but not lysosome. MRL828 treatment led autophagosome-dependent secretion oligomeric species, suggesting reduction secretory autophagy rather than This work highlights mechanism action (MOA) ALP-based molecule potential new strategy cellular removal interest.

Язык: Английский

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Extracellular Vesicles in the Crosstalk of Autophagy and Apoptosis: A Role for Lipid Rafts

Cells, Год журнала: 2025, Номер 14(10), С. 749 - 749

Опубликована: Май 20, 2025

Autophagy and apoptosis are two essential mechanisms regulating cell fate. Although distinct, their signaling pathways closely interconnected through various crosstalk mechanisms. Lipid rafts described to act as both physical functional platforms during the early stages of autophagic apoptotic processes. Only recently has a role for lipid raft-associated molecules in EV biogenesis release begun emerge. In particular, lipids membranes components conferring stability these vesicles different extracellular environments and/or facilitate binding or uptake into recipient cells. this review we highlight aspects, focusing on secretory autophagy pathways. We describe molecular machinery that connects with vesicular trafficking metabolism EVs, how alterations contribute development diseases, including autoimmune disorders cancer. Overall, findings emphasize complexity autophagy/apoptosis its key cellular dynamics, supporting new therapeutic targets.

Язык: Английский

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Autophagy unraveled: Navigating cell fate and disease dynamics

Biochemistry and Biophysics Reports, Год журнала: 2024, Номер 39, С. 101752 - 101752

Опубликована: Июнь 1, 2024

Язык: Английский

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