Whole‐Cell Lysosome SMLM Imaging as Indicators for Functional Diagnostics with a Low‐Phototoxic Spontaneously Blinking Probe DOI Open Access
Qinglong Qiao, Aimin Song, Guanyu Jiang

et al.

Angewandte Chemie International Edition, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Abstract Lysosomal morphology and pH dynamics are key indicators of lysosomal function, making long‐term single‐molecule localization microscopy (SMLM) imaging a promising tool for functional diagnostics. However, phototoxicity often compromises reliability. Here, we develop Aze‐HMSiR , spontaneously blinking silicon rhodamine probe with near‐infrared excitation, enabling low‐phototoxicity, (50 min) SMLM dynamics. This provides super‐resolution insights into distribution, size, lumen pH, essential understanding their physiological pathological roles. Using investigate function under acidosis, starvation, anticancer drug treatments. Among seven tested drugs, periplocoside significantly reduced while paclitaxel increased altered distribution. These findings highlight as powerful diagnostics screening, offering robust platform studying in response to pharmacological perturbations, particularly cancer therapy.

Language: Английский

Lipid metabolism, remodelling and intercellular transfer in the CNS DOI
Sam Vanherle, Melanie Loix, Véronique E. Miron

et al.

Nature reviews. Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Language: Английский

Citations

3
Autophagy–lysosomal-associated neuronal death in neurodegenerative disease DOI
Ralph A. Nixon

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 148(1)

Published: Sept. 11, 2024

Language: Английский

Citations

14
Pathobiology of the autophagy-lysosomal pathway in the Huntington’s disease brain DOI Open Access
Martin J. Berg,

Veeranna,

Corrinne M. Rosa

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 30, 2024

Abstract Accumulated levels of mutant huntingtin protein (mHTT) and its fragments are considered contributors to the pathogenesis Huntington’s disease (HD). Although lowering mHTT by stimulating autophagy has been a possible therapeutic strategy, role competence autophagy-lysosomal pathway (ALP) during HD progression in human remains largely unknown. Here, we used multiplex confocal ultrastructural immunocytochemical analyses ALP functional markers relation aggresome pathology striatum less affected cortex brains staged from HD2 HD4 Vonsattel neuropathological criteria compared controls. Immunolabeling revealed localization HTT/mHTT vesicular compartments labeled autophagy-related adaptor proteins p62/SQSTM1 ubiquitin, cathepsin D (CTSD) as well HTT-positive inclusions. comparatively normal at HD2, neurons later stages exhibited progressive enlargement clustering CTSD-immunoreactive autolysosomes/lysosomes and, ultrastructurally, autophagic vacuole/lipofuscin granules accumulated progressively, more prominently than cortex. These changes were accompanied rises p62/SQSTM1, particularly their fragments, but not cortex, increases LAMP1 LAMP2 RNA protein. Importantly, no blockage autophagosome formation autophagosome-lysosome fusion was detected, thus pinpointing substrate clearance deficits basis for flux declines. The findings collectively suggest that upregulated lysosomal biogenesis preserved proteolysis maintain early-stage HD, failure advanced contributes HTT build-up potential neurotoxicity. support prospect stimulation applied early stages, when machinery is fully competent, may have benefits patients.

Language: Английский

Citations

10
Canonical and noncanonical autophagy: involvement in Parkinson’s disease DOI Creative Commons
Maria Sakurai, Tomoki Kuwahara

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 30, 2025

Autophagy is the major degradation process in cells and involved a variety of physiological pathological functions. While macroautophagy, which employs series molecular cascades to form ATG8-coated double membrane autophagosomes for degradation, remains well-known type canonical autophagy, microautophagy chaperon-mediated autophagy have also been characterized. On other hand, recent studies focused on functions proteins beyond intracellular including noncanonical known as conjugation ATG8 single membranes (CASM), autophagy-related extracellular secretion. In particular, CASM unique that it does not require upstream mechanisms, while system manner different from autophagy. There many reports involvement these mechanisms neurodegenerative diseases, with Parkinson’s disease (PD) receiving particular attention because important roles several causative risk genes, LRRK2. this review, we will summarize discuss contributions cellular functions, special focus pathogenesis PD.

Language: Английский

Citations

2
Relationship between enriched environment and neurodegeneration: a review from mechanism to therapy DOI Creative Commons
Yang Xu, YangQuan Chen,

Jia‐xin Xing

et al.

Clinical Epigenetics, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 24, 2025

Enriched environment (EE), as a non-pharmacological intervention, has garnered considerable attention for its potential to ameliorate neurodegenerative diseases (NDs). This review delineated the impact of EE on biological functions associated with NDs, emphasizing role in enhancing neural plasticity, reducing inflammation, and bolstering cognitive performance. We discussed molecular underpinnings effects EE, including modulation key signaling pathways such extracellular regulated kinase 1/2 (ERK1/2), mitogen-activated protein kinases (MAPK), AMPK/SIRT1, which were implicated neuroprotection synaptic plasticity. Additionally, we scrutinized influence epigenetic modifications autophagy, processes pivotal ND pathogenesis. Animal models, encompassing both rodents larger animals, offer insights into disease-modifying underscoring complementary approach pharmacological interventions. In summary, emerges promising strategy augment function decelerate progression NDs.

Language: Английский

Citations

1
N7-methylguanosine modification in cancers: from mechanisms to therapeutic potential DOI Creative Commons
Qihui Wu, Xiaodan Fu,

Guoqian Liu

et al.

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 29, 2025

N7-methylguanosine (m7G) is an important RNA modification involved in epigenetic regulation that commonly observed both prokaryotic and eukaryotic organisms. Their influence on the synthesis processing of messenger RNA, ribosomal transfer allows m7G modifications to affect diverse cellular, physiological, pathological processes. are pivotal human diseases, particularly cancer progression. On one hand, modification-associated modulate tumour progression malignant biological characteristics, including sustained proliferation signalling, resistance cell death, activation invasion metastasis, reprogramming energy metabolism, genome instability, immune evasion. This suggests they may be novel therapeutic targets for treatment. other aberrant expression molecules linked clinicopathological staging, lymph node unfavourable prognoses patients with cancer, indicating their potential as biomarkers. review consolidates discovery, identification, detection methodologies, functional roles modification, analysing mechanisms by which contribute development, exploring clinical applications diagnostics therapy, thereby providing innovative strategies identification targeted

Language: Английский

Citations

1
Multi-omics analyses reveal that Sirtuin 5 promotes the development of pre-recruitment follicles by inhibiting the autophagy-lysosome pathway in chicken granulosa cells DOI Creative Commons

Ruotong Zou,

Li Wang,

Xi Zhang

et al.

Poultry Science, Journal Year: 2025, Volume and Issue: 104(3), P. 104884 - 104884

Published: Feb. 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.

Language: Английский

Citations

1
Autophagy-dependent versus autophagy-independent ferroptosis DOI Creative Commons

Ye Zhu,

Motoki Fujimaki,

David C. Rubinsztein

et al.

Trends in Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Ferroptosis is an iron-dependent cell death pathway that, until recently, has been considered to be dependent on autophagy. However, recent studies have reported conflicting results, raising the question about which contexts determine roles of autophagy in ferroptosis. This opinion article addresses this by summarizing and/or diseases a driver or suppressor The execution ferroptosis depends levels (labile) iron, unsaturated (phospho)lipids and free radicals. We propose that context these three factors their upstream pathways are differentially regulated dictates whether positively negatively regulates

Language: Английский

Citations

1
Abnormal epigenetic modification of lysosome and lipid regulating genes in Alzheimer’s disease DOI Creative Commons

Tingting Ruan,

Yunxiang Ling,

Can Wu

et al.

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Background Abnormal lipid metabolism has been identified as a potential pathogenic mechanism of Alzheimer's disease (AD), which might be epigenetically regulated. Lysosomes are critical organelles for metabolism. However, the epigenetic modifications lysosome and regulating genes remain unclear in AD patients. Objective Explore role abnormal modifications, especially methylation metabolism-related AD. Methods Methylation beadchip MALDI-TOF mass spectrometry were used to detect genome-wide DNA levels validate key gene methylation, respectively. Clinical data collected from all participants. Associations between clinical biochemical characteristics altered patients analyzed, risk factor model was established. Results 41 differentially methylated positions (DMPs) corresponding 33 patients, with 18 hypermethylated 23 hypomethylated positions. Significant alterations observed ( CTNNB1, DGKQ, SLC27A1 ) lysosomal transmembrane TMEM175 ). analysis revealed that TP, ALB, IB, ADA, ALP, HCY, GLU, TC, BUN, HDL-C, LDL-C, APOA1 significantly higher whereas A/G DB lower. hypermethylation further verified found correlate APOA1, HCY. The AUC model, integrated markers reached 0.9519 p < 0.0001). Conclusions regulation dyshomeostasis high-risk factors processes pathogenesis.

Language: Английский

Citations

1
Targeting neurodegenerative disease-associated protein aggregation with proximity-inducing modalities DOI

Ruixin Ge,

Miao Chen, Qingchao Li

et al.

Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Language: Английский

Citations

1