Nanomedicine Approaches for Autophagy Modulation in Cancer Therapy DOI Creative Commons

Sohaib Mahri,

Raffaella Villa,

Ya‐Ping Shiau

и другие.

Small Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 11, 2025

Cancer is a daunting global health problem with steadily rising incidence. Despite the wide arsenal of current anticancer therapies, challenges such as drug resistance, tumor heterogeneity, poor targeting, and severe side effects often lead to suboptimal efficacy patient outcomes, highlighting need for innovative therapies. Autophagy modulation has emerged an attractive approach complement existing The dual role autophagy in cancer promotion suppression inspired development new drugs therapeutic strategies focusing on both inhibition induction. promising results modulators preclinical studies, lack selectivity potency, toxicity, pharmacokinetics, inadequate targeting continue limit their successful clinical translation. Many these could be overcome using nanomedicine. This review explores recent advancements nanomedicine modulation. Successful combination leveraging nanoparticles synergy chemotherapy, immunotherapy, phototherapy, gene therapy, other modalities are presented. Additionally, nanomaterials intrinsic autophagy‐modulating capabilities, self‐assembling inhibitors, discussed. Finally, limitations currently trials discussed, future perspectives designing implementation explored.

Язык: Английский

Autophagy-driven regulation of cisplatin response in human cancers: Exploring molecular and cell death dynamics DOI Creative Commons
Yang Yang,

Lixia Liu,

Yu Tian

и другие.

Cancer Letters, Год журнала: 2024, Номер 587, С. 216659 - 216659

Опубликована: Фев. 15, 2024

Despite the challenges posed by drug resistance and side effects, chemotherapy remains a pivotal strategy in cancer treatment. A key issue this context is macroautophagy (commonly known as autophagy), dysregulated cell death mechanism often observed during chemotherapy. Autophagy plays cytoprotective role maintaining cellular homeostasis recycling organelles, emerging evidence points to its significant promoting progression. Cisplatin, DNA-intercalating agent for inducing cycle arrest, encounters treatments. Recent studies have shown that autophagy can contribute cisplatin or insensitivity tumor cells through various mechanisms. This be mediated protective autophagy, which suppresses apoptosis. Additionally, autophagy-related changes metastasis, particularly induction of Epithelial-Mesenchymal Transition (EMT), also lead resistance. Nevertheless, pharmacological strategies targeting regulation apoptosis offer promising avenues enhance sensitivity therapy. Notably, numerous non-coding RNAs been identified regulators Thus, therapeutic associated pathways holds potential restoring sensitivity, highlighting an important direction future clinical research.

Язык: Английский

Процитировано

71
Autophagy in health and disease: From molecular mechanisms to therapeutic target DOI Creative Commons
Guang Lu, Yu Wang, Yin Shi

и другие.

MedComm, Год журнала: 2022, Номер 3(3)

Опубликована: Июль 10, 2022

Macroautophagy/autophagy is an evolutionally conserved catabolic process in which cytosolic contents, such as aggregated proteins, dysfunctional organelle, or invading pathogens, are sequestered by the double-membrane structure termed autophagosome and delivered to lysosome for degradation. Over past two decades, autophagy has been extensively studied, from molecular mechanisms, biological functions, implications various human diseases, development of autophagy-related therapeutics. This review will focus on latest research, covering mechanisms control biogenesis autophagosome-lysosome fusion, upstream regulatory pathways including AMPK MTORC1 pathways. We also provide a systematic discussion implication cancer, neurodegenerative disorders (Alzheimer disease, Parkinson Huntington's Amyotrophic lateral sclerosis), metabolic diseases (obesity diabetes), viral infection especially SARS-Cov-2 COVID-19, cardiovascular (cardiac ischemia/reperfusion cardiomyopathy), aging. Finally, we summarize pharmacological agents that have therapeutic potential clinical applications via targeting pathway. It believed decades hard work research eventually bring real tangible benefits improvement health diseases.

Язык: Английский

Процитировано

69
Recent Update and Drug Target in Molecular and Pharmacological Insights into Autophagy Modulation in Cancer Treatment and Future Progress DOI Creative Commons
Md. Ataur Rahman, Abu Saim Mohammad Saikat, Md Saidur Rahman

и другие.

Cells, Год журнала: 2023, Номер 12(3), С. 458 - 458

Опубликована: Янв. 31, 2023

Recent evidence suggests that autophagy is a governed catabolic framework enabling the recycling of nutrients from injured organelles and other cellular constituents via lysosomal breakdown. This mechanism has been associated with development various pathologic conditions, including cancer neurological disorders; however, recently updated studies have indicated plays dual role in cancer, acting as cytoprotective or cytotoxic mechanism. Numerous preclinical clinical investigations shown inhibiting enhances an anticancer medicine’s effectiveness malignancies. Autophagy antagonists, chloroquine hydroxychloroquine, previously authorized trials, encouraging medication-combination therapies targeting autophagic processes for cancer. In this review, we provide update on recent research examining efficacy combining drugs activate inhibitors. Additionally, highlight difficulties progress toward using treatment strategy. Importantly, must enable use suitable inhibitors coadministration delivery systems conjunction agents. Therefore, review briefly summarizes general molecular process behind its bifunctional important suppression tumor growth resistance to chemotherapy metastasis regulation. We then emphasize how cells interacting one another promising therapeutic target treatment.

Язык: Английский

Процитировано

27
Humanin and Its Pathophysiological Roles in Aging: A Systematic Review DOI Creative Commons
Donatella Coradduzza, Antonella Congiargiu, Zhichao Chen

и другие.

Biology, Год журнала: 2023, Номер 12(4), С. 558 - 558

Опубликована: Апрель 6, 2023

Background: Senescence is a cellular aging process in all multicellular organisms. It characterized by decline functions and proliferation, resulting increased damage death. These conditions play an essential role significantly contribute to the development of age-related complications. Humanin mitochondrial-derived peptide (MDP), encoded mitochondrial DNA, playing cytoprotective preserve function cell viability under stressful senescence conditions. For these reasons, humanin can be exploited strategies aiming counteract several processes involved aging, including cardiovascular disease, neurodegeneration, cancer. Relevance disease: appears decay organ tissue function, it has also been related diseases, such as conditions, cancer, diabetes. In particular, senescent cells produce inflammatory cytokines other pro-inflammatory molecules that participate diseases. Humanin, on hand, seems contrast known diseases promoting death damaged or malfunctioning contributing inflammation often associated with them. Both humanin-related mechanisms are complex have not fully clarified yet. Further research needed thoroughly understand disease identify potential interventions target them order prevent treat Objectives: This systematic review aims assess underlying link connecting senescence, humanin, disease.

Язык: Английский

Процитировано

25
Spautin-1 promotes PINK1-PRKN-dependent mitophagy and improves associative learning capability in an alzheimer disease animal model DOI Creative Commons
Juan Yi, Heling Wang, Guang Lu

и другие.

Autophagy, Год журнала: 2024, Номер 20(12), С. 2655 - 2676

Опубликована: Июль 25, 2024

Spautin-1 is a well-known macroautophagy/autophagy inhibitor via suppressing the deubiquitinases USP10 and USP13 promoting degradation of PIK3C3/VPS34-BECN1 complex, while its effect on selective autophagy remains poorly understood. Mitophagy form for removal damaged superfluous mitochondria autophagy-lysosome pathway. Here, we report surprising discovery that, spautin-1 as an effective inhibitor, it promotes PINK1-PRKN-dependent mitophagy induced by mitochondrial damage agents. Mechanistically, facilitates stabilization activation full-length PINK1 at outer membrane (OMM) binding to components TOMM complex (TOMM70 TOMM20), leading disruption import prevention PARL-mediated cleavage. Moreover, induces neuronal in

Язык: Английский

Процитировано

10
PROTACs in the treatment of viral diseases DOI Creative Commons
Ritesh P. Bhole, Payal R. Kute, Shailendra Gurav

и другие.

Future Medicinal Chemistry, Год журнала: 2025, Номер 17(3), С. 267 - 269

Опубликована: Янв. 15, 2025

KEYWORDS: PROTACsAntiviral therapyUbiquitin-proteasome systemUndruggable targetsDrug resistanceIndomethacin-based PROTACsViral diseasesPROTACs in clinical trials

Язык: Английский

Процитировано

1
The Role of Intermittent Fasting in the Management of Nonalcoholic Fatty Liver Disease: A Narrative Review DOI Open Access
Celeste M. Lavallee, Andreina Bruno, Christopher Ma

и другие.

Nutrients, Год журнала: 2022, Номер 14(21), С. 4655 - 4655

Опубликована: Ноя. 3, 2022

Intermittent fasting is a non-pharmacological dietary approach to management of obesity and metabolic syndrome, involving periodic intervals complete or near-complete abstinence from food energy-containing fluids. This strategy has recently gained significant popularity in mainstream culture been shown induce weight loss humans, reduce gut systemic inflammation, improve microbial diversity dysbiosis (largely animal models). It hypothesized that intermittent could be beneficial the nonalcoholic fatty liver disease, given condition's association with obesity. review summarizes protocols, potential mechanisms action, evidence for disease. also highlights practical considerations implementing clinical practice. A search literature English-language articles related time-restricted feeding disease was completed PubMed Google Scholar. Potential action effects included modulation circadian rhythm, adipose tissue adipokines, microbiome, autophagy. Preclinical, epidemiological, trial data suggested benefits on inflammatory markers humans. However, there paucity its patients More studies are needed determine evaluate safety efficacy this population.

Язык: Английский

Процитировано

31
Autophagy Requirements for Eye Lens Differentiation and Transparency DOI Creative Commons
Lisa Brennan, M. Joseph Costello, J. Fielding Hejtmancik

и другие.

Cells, Год журнала: 2023, Номер 12(3), С. 475 - 475

Опубликована: Фев. 1, 2023

Recent evidence points to autophagy as an essential cellular requirement for achieving the mature structure, homeostasis, and transparency of lens. Collective from multiple laboratories using chick, mouse, primate, human model systems provides that classic structures, ranging double-membrane autophagosomes single-membrane autolysosomes, are found throughout lens in both undifferentiated epithelial cells maturing fiber cells. Recently, key signaling pathways have been identified initiate critical steps differentiation program, including elimination organelles form core organelle-free zone. Other recent studies ex vivo culture demonstrate low oxygen environment drives HIF1a-induced via upregulation mitophagy components direct specific mitochondria, endoplasmic reticulum, Golgi apparatus during cell differentiation. Pioneering on structural requirements nuclei reveal presence entirely novel structure associated with degrading termed nuclear excisosome. Considerable also indicates is a differentiation, transparency, since mutation proteins results cataract formation.

Язык: Английский

Процитировано

18
Autophagy and neurodegeneration: Unraveling the role of C9ORF72 in the regulation of autophagy and its relationship to ALS-FTD pathology DOI Creative Commons

Rim Diab,

Federica Pilotto, Smita Saxena

и другие.

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Март 16, 2023

The proper functioning of the cell clearance machinery is critical for neuronal health within central nervous system (CNS). In normal physiological conditions, actively involved in elimination misfolded and toxic proteins throughout lifetime an organism. highly conserved regulated pathway autophagy one important processes preventing neutralizing pathogenic buildup that could eventually lead to development neurodegenerative diseases (NDs) such as Alzheimer's disease or Amyotrophic lateral sclerosis (ALS). most common genetic cause ALS frontotemporal dementia (FTD) a hexanucleotide expansion consisting GGGGCC (G4C2) repeats chromosome 9 open reading frame 72 gene (C9ORF72). These abnormally expanded have been implicated leading three main modes pathology: loss function C9ORF72 protein, generation RNA foci, production dipeptide repeat (DPRs). this review, we discuss role autophagy-lysosome (ALP), present recent research deciphering how dysfunction ALP synergizes with haploinsufficiency, which together gain mechanisms involving expansions DPRs, drive process. This review delves further into interactions RAB endosomal/lysosomal trafficking, their regulating various steps lysosomal pathways. Lastly, aims provide framework investigations C9ORF72-linked ALS-FTD well other diseases.

Язык: Английский

Процитировано

18
Molecular regulation and therapeutic implications of cell death in pulmonary hypertension DOI Creative Commons
Enze Wang,

Sijing Zhou,

Daxiong Zeng

и другие.

Cell Death Discovery, Год журнала: 2023, Номер 9(1)

Опубликована: Июль 12, 2023

Abstract Pulmonary hypertension (PH) is a clinical and pathophysiological syndrome caused by changes in pulmonary vascular structure or function that results increased resistance arterial pressure, it characterized endothelial dysfunction, artery media thickening, remodeling, right ventricular hypertrophy, all of which are driven an imbalance between the growth death cells. Programmed cell (PCD), different from necrosis, active cellular mechanism activated response to both internal external factors precisely regulated More than dozen PCD modes have been identified, among apoptosis, autophagy, pyroptosis, ferroptosis, necroptosis, cuproptosis proven be involved pathophysiology PH varying degrees. This article provides summary regulatory patterns their potential effects on PH. Additionally, describes current understanding this complex interconnected process analyzes therapeutic targeting specific as molecular targets.

Язык: Английский

Процитировано

17