Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson’s Disease with Potential Therapeutic Implications

Biomolecules, Год журнала: 2025, Номер 15(1), С. 149 - 149

Опубликована: Янв. 19, 2025

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder marked by the progressive degeneration of midbrain dopaminergic neurons and resultant locomotor dysfunction. Despite over two centuries recognition as chronic disease, exact pathogenesis PD remains elusive. The onset progression involve multiple complex pathological processes, with dysfunctional autophagy elevated oxidative stress serving critical contributors. Notably, emerging research has underscored interplay between in pathogenesis. Given limited efficacy therapies targeting either dysfunction or stress, it crucial to elucidate intricate mechanisms governing their develop more effective therapeutics. This review overviews role nuclear factor erythroid 2-related 2 (Nrf2), pivotal transcriptional regulator orchestrating cellular defense against these processes. By elucidating key processes PD, this will deepen our comprehensive understanding multifaceted underlying may uncover potential strategies for its prevention treatment.

Язык: Английский

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Double‐pronged Antimicrobial Agents based on a Donor‐π‐Acceptor Type Aggregation‐Induced Emission Luminogen

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(47)

Опубликована: Сен. 30, 2022

Abstract Novel antibacterial agents are urgently needed to control the infections induced by multidrug‐resistant (MDR) bacteria. Herein, we rationally designed and facilely synthesized a new D‐π‐A type luminogen with strong red/near‐infrared fluorescence emission, great aggregation‐induced emission (AIE) features, excellent reactive oxygen species (ROS) production. The newly developed molecule TTTh killed methicillin‐resistant Staphylococcus aureus (MRSA) triggering ROS accumulation in bacteria interrupting membrane integrity. Moreover, specifically targeted lysosomes potentiated their maturation accelerate clearance of intracellular Additionally, reduced bacterial burden improved healing were observed TTTh‐treated wounds negligible side effects. Our study expands biological design application AIE luminogens (AIEgens), provides insights into discovering novel targets agents.

Язык: Английский

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Lysosome signaling in cell survival and programmed cell death for cellular homeostasis

Journal of Cellular Physiology, Год журнала: 2022, Номер 238(2), С. 287 - 305

Опубликована: Дек. 11, 2022

Abstract Recent developments in lysosome biology have transformed our view of lysosomes from static garbage disposals that can also act as suicide bags to decidedly dynamic multirole adaptive operators cellular homeostasis. Lysosome‐governed signaling pathways, proteins, and transcription factors equilibrate the rate catabolism anabolism (autophagy lysosomal biogenesis metabolite pool maintenance) by sensing metabolic status. Lysosomes interact with other organelles establishing contact sites through which they exchange contents. Lysosomal function is critically assessed positioning motility for adaptation. In this setting, mechanistic target rapamycin kinase (MTOR) chief architect control Notably, orchestrate explicit cell death mechanisms, such autophagic membrane permeabilization‐associated regulated necrotic death, maintain These lines evidence emphasize serve a central hub

Язык: Английский

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Autophagy in sarcopenia: Possible mechanisms and novel therapies

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 165, С. 115147 - 115147

Опубликована: Июль 18, 2023

With global population aging, age-related diseases, especially sarcopenia, have attracted much attention in recent years. Characterized by low muscle strength, quantity or quality and physical performance, sarcopenia is one of the major factors associated with an increased risk falls disability. Much effort has been made to understand cellular biological physiological mechanisms underlying sarcopenia. Autophagy important self-protection mechanism that relies on lysosomes degrade misfolded proteins damaged organelles. Research designed obtain new insight into human diseases from autophagic aspect carried out progress, which encourages relevant studies relationship between autophagy plays a protective role modulating regenerative capability satellite cells, relieving oxidative stress suppressing inflammatory response. This review aims reveal specific interaction explore possible therapies hopes encouraging more research need unlocking novel promising ameliorate

Язык: Английский

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Mitochondria‐associated endoplasmic reticulum membrane: Overview and inextricable link with cancer

Journal of Cellular and Molecular Medicine, Год журнала: 2023, Номер 27(7), С. 906 - 919

Опубликована: Фев. 27, 2023

Abstract The mitochondrial‐associated membrane (MAM) is a physical platform that facilitates communication between the endoplasmic reticulum (ER) and mitochondria. It enriched with many proteins enzymes plays an important role in regulation of several fundamental physiological processes, such as calcium (Ca 2+ ) transfer, lipid synthesis, cellular autophagy ER stress. Accumulating evidence suggests oncogenes suppressor genes are present at ER‐mitochondrial contact site, their alterations can affect Ca flux, homeostasis, dysregulation mitochondrial dynamics, thereby influencing fate cancer cells. Understanding MAM‐resident tumorigenesis could support search for novel therapeutic targets cancer. In this review, we summarize basic structure MAM core functions tumorigenesis. addition, discuss mechanisms by which natural compounds promote cell apoptosis from perspective

Язык: Английский

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The HN protein of Newcastle disease virus induces cell apoptosis through the induction of lysosomal membrane permeabilization

PLoS Pathogens, Год журнала: 2024, Номер 20(2), С. e1011981 - e1011981

Опубликована: Фев. 14, 2024

Lysosomes are acidic organelles that mediate the degradation and recycling of cellular waste materials. Damage to lysosomes can cause lysosomal membrane permeabilization (LMP) trigger different types cell death, including apoptosis. Newcastle disease virus (NDV) naturally infect most birds. Additionally, it serves as a promising oncolytic known for its effective infection tumor cells induction intensive apoptotic responses. However, involvement in NDV-induced apoptosis remains poorly understood. Here, we demonstrate NDV profoundly triggers LMP, leading translocation cathepsin B D subsequent mitochondria-dependent various avian cells. Notably, released exacerbate LMP by inducing generation reactive oxygen species. uncover viral Hemagglutinin neuraminidase (HN) protein induces deglycosylation lysosome-associated 1 (LAMP1) LAMP2 dependent on sialidase activity, which finally contributes Overall, our findings elucidate role provide novel insights into function HN during innovative approaches development NDV-based agents.

Язык: Английский

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Fraxinellone-mediated targeting of cathepsin B leakage from lysosomes induces ferroptosis in fibroblasts to inhibit hypertrophic scar formation

Biology Direct, Год журнала: 2025, Номер 20(1)

Опубликована: Фев. 4, 2025

Hypertrophic scar (HS) is a common fibrotic skin disorder characterized by the excessive deposition of extracellular matrix (ECM). Fibroblasts are most important effector cells involved in HS formation. Currently no satisfactory treatment has been developed. The impact fraxinellone (FRA) on proliferation and migration capacity human hypertrophic scar-derived fibroblasts (HSFs) was assessed EdU proliferation, wound healing transwell assays. Quantitative real-time PCR (qRT‒PCR), Western blot (WB), immunofluorescence staining collagen gel contraction assays were performed to evaluate production activation HSFs. Oxford Nanopore Technologies long-read RNA sequencing (ONT RNA-seq) revealed occurrence ferroptosis HSF executioner-cathepsin B (CTSB). mechanisms underlying FRA-induced examined through fluorescence staining, qRT‒PCR, WB molecular docking study. therapeutic efficacy FRA further validated vivo using rabbit ear model. significantly suppressed migration, ONT RNA-seq discovered that modulated expression transcripts related lysosomes. Mechanistically, reduced protein level glutathione peroxidase 4 (GPX4) induced release CTSB from lysosomes into cytoplasm. via spermidine/spermine-N1-acetyltransferase (SAT1)-mediated lipid peroxidation, mitochondrial damage mitogen-activated kinase (MAPK) signalling pathway activation, eventually affecting function Moreover, attenuated formation ears CTSB-mediated ferroptosis. antifibrotic effects abrogated pretreatment with inhibitor (CA-074-me). This study reveals ameliorates inducing leakage lysosomes, causing SAT1-mediated MAPK thus mediating Therefore, could be promising agent for treating HS.

Язык: Английский

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Combating chemoresistance: Current approaches & nanocarrier mediated targeted delivery

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2025, Номер unknown, С. 189261 - 189261

Опубликована: Янв. 1, 2025

Язык: Английский

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Melanoma bone metastasis-induced osteocyte ferroptosis via the HIF1α-HMOX1 axis

Bone Research, Год журнала: 2025, Номер 13(1)

Опубликована: Янв. 16, 2025

Abstract Osteocytes are the main cells in mineralized bone tissue. Elevated osteocyte apoptosis has been observed lytic lesions of patients with multiple myeloma. However, their precise contribution to metastasis remains unclear. Here, we investigated pathogenic mechanisms driving melanoma-induced death. Both vivo models and vitro assays were combined untargeted RNA sequencing approaches explore pathways governing We could show that ferroptosis is primary mechanism behind death context melanoma metastasis. HMOX1 was identified as a crucial regulatory factor this process, directly involved inducing affecting viability. uncover non-canonical pathway involves excessive autophagy-mediated ferritin degradation, highlighting complex relationship between autophagy In addition, HIF1α shown an upstream regulator, providing potential target for modulating expression influencing autophagy-dependent ferroptosis. conclusion, our study provides insight into induced by metastasis, specific focus on its regulation. This would enhance comprehension

Язык: Английский

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Multi-omics analyses reveal that Sirtuin 5 promotes the development of pre-recruitment follicles by inhibiting the autophagy-lysosome pathway in chicken granulosa cells

Poultry Science, Год журнала: 2025, Номер 104(3), С. 104884 - 104884

Опубликована: Фев. 7, 2025

The development of pre-recruitment follicles plays a critical role in determining egg-laying performance poultry. This study combines proteomic and metabolomic analyses to explore changes proteins metabolites, elucidate key regulatory mechanism involved chicken follicular development. Histological examination revealed significant increase yolk deposition small yellow (SYF) compared white (SWF). Metabolomics analysis identified significantly enriched differential metabolites (DMs) between SWF SYF pathways such as Lysosome, Ferroptosis, Biosynthesis unsaturated fatty acids, Tryptophan metabolism. Particularly, Adenosine-5'-Diphosphate (ADP) was downregulated during recruitment the lysosome pathway. Proteomic that differentially expressed (DEPs) were including Glutathione metabolism, Cholesterol Arginine proline amino acid biosynthesis. Among these DEPs, NAD-dependent protein deacetylase sirtuin 5 (SIRT5) upregulated, while lysosomal-associated membrane 1 (LAMP1) down-regulated follicles. SIRT5 linked negative regulation reactive oxygen species whereas LAMP1 associated with autophagy pathways. Further validation experiments demonstrated high expression SYF, particularly granulosa cells (GCs). Silencing GCs resulted increased ROS production upregulated autophagy-related LC3Ⅱ Beclin1, well markers LAMP1. Conversely, lipid droplet p62 suppressed. inhibited. Taken together, findings suggest upregulation promotes by inhibiting autophagy-lysosome pathway GCs.

Язык: Английский

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