Autophagy reports最新文献_第2页

Autophagy in alzheimer disease pathogenesis and its therapeutic values. 自噬在阿尔茨海默病发病机制中的作用及其治疗价值。

Autophagy reports Pub Date : 2025-05-08 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2471677

Gabrielle Angst, Nuo Jia, Luis E Tron Esqueda, Yanbo Fan, Qian Cai, Chenran Wang

{"title":"Autophagy in alzheimer disease pathogenesis and its therapeutic values.","authors":"Gabrielle Angst, Nuo Jia, Luis E Tron Esqueda, Yanbo Fan, Qian Cai, Chenran Wang","doi":"10.1080/27694127.2025.2471677","DOIUrl":"10.1080/27694127.2025.2471677","url":null,"abstract":"Alzheimer disease (AD) is the most common form of dementia with hallmarks of β-amyloid deposits, neurofilament tangles, synaptic loss and neuronal death in the patient's brain. AD is a heavy burden in an ageing society as there are no effective therapies in treating the causes or slowing down its progression. Autophagy is a conserved process through formation of double membrane structure, namely autophagosome which is delivered to lysosome to digest cellular disposals. Autophagy maintains homoeostasis in the brain and is generally considered to protect brain functions against ageing. The first evidence of autophagy involvement in AD is that there is decreased expression of autophagy essential genes in post-mortem AD brains. Autophagy is also believed to be protective in neurodegeneration. However, the molecular and cellular mechanisms for dysfunction of autophagy in AD are not fully understood. Recent studies of autophagy regulation in AD cover the findings not only in neurons, but also from fast growing evidence for their importance in glia and brain vascular system. Thus, this review composes pertinent information regarding the involvement of autophagy in neurons, glias (including microglia, astrocyte, and oligodendrocyte), and brain vascular cells in AD, and their unique cellular mechanisms of this connection in AD pathology. We will provide effectual insights both in investigating autophagy in AD pathological mechanisms and in establishing a strategic approach for developing autophagy-based AD therapies.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2471677"},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Amino acid storage: lysosomal double role in health and disease. 氨基酸储存：溶酶体在健康和疾病中的双重作用。

Autophagy reports Pub Date : 2025-05-08 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2498324

Aiswarya Raj, Samantha Shrihari, Urmi Bandyopadhyay

{"title":"Amino acid storage: lysosomal double role in health and disease.","authors":"Aiswarya Raj, Samantha Shrihari, Urmi Bandyopadhyay","doi":"10.1080/27694127.2025.2498324","DOIUrl":"10.1080/27694127.2025.2498324","url":null,"abstract":"Cellular homeostasis depends on a multitude of cellular functions, which in turn depend on the clearance of damaged components for their maintenance. Lysosomes being one of the main sites of recycling, are at the frontline for cellular protein degradation, which leads to generation of protein building blocks, the amino acids (AAs), within the lysosomal lumen. However, the fate of these lysosomal pool of AAs are only partly known. Recently, studies from our and other groups have led to the finding that AA can be stored in lysosomes and revealed a homeostatic communication of these storages with the environment. Thus, lysosome appear to be a nutritional signaling hub that has a dual role. As a degradation-competent hydrolytic sack, lysosomes have a long-studied degradative function, additionally now they can either store or channel into utilization of the AAs generated through their proteolytic activity. Since the existence of a lysosomal AA storage pool has been determined by changing the levels of extracellular AAs, this indicates a multi-directional homeostatic communication between the lysosome and the extracellular environment. This Lysosomal homeostatic and adaptive response to the niche could be vital for life-threatening age-related degenerative disorders, where the lysosome-autophagy pathway and the microenvironmental cues play major roles in the disease progression, which will be discussed further in this piece.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2498324"},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BECLIN-1 is essential for the maintenance of gastrointestinal epithelial integrity by regulating endocytic trafficking, F-actin organization, and lysosomal function. BECLIN-1通过调节内吞运输、f -肌动蛋白组织和溶酶体功能，对维持胃肠道上皮完整性至关重要。

Autophagy reports Pub Date : 2025-04-03 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2484494

Juliani Juliani, Sharon Tran, Tiffany J Harris, Peter De Cruz, Sarah L Ellis, Paul A Gleeson, John M Mariadason, Kinga Duszyc, Alpha S Yap, Erinna F Lee, Walter D Fairlie

{"title":"BECLIN-1 is essential for the maintenance of gastrointestinal epithelial integrity by regulating endocytic trafficking, F-actin organization, and lysosomal function.","authors":"Juliani Juliani, Sharon Tran, Tiffany J Harris, Peter De Cruz, Sarah L Ellis, Paul A Gleeson, John M Mariadason, Kinga Duszyc, Alpha S Yap, Erinna F Lee, Walter D Fairlie","doi":"10.1080/27694127.2025.2484494","DOIUrl":"10.1080/27694127.2025.2484494","url":null,"abstract":"Disrupted intestinal homeostasis and barrier function contribute to the development of diseases such as inflammatory bowel disease. BECLIN-1, a core component of two class III phosphatidylinositol 3 kinase complexes, has a dual role in autophagy and endocytic trafficking. Emerging evidence suggests that its endocytic trafficking function is essential for intestinal integrity. To investigate the fatal gastrointestinal phenotype observed in BECLIN-1 knockout mice, we used organoids derived from these animals to show that BECLIN-1 deletion disrupts the localization of CADHERIN1/ECADHERIN to adherens junctions and OCCLUDIN to tight junctions. Impaired cargo trafficking to the lysosome was also observed. Filamentous actin cytoskeleton also became disorganized though there were no changes in its spatial interaction with CATENIN BETA1/BETA-CATENIN nor in BETA-CATENIN localization. The trafficking defects were all less pronounced or absent in organoids lacking an autophagy-only regulator, ATG7, emphasizing BECLIN-1's trafficking role in maintaining gut homeostasis and barrier function. These findings advance our understanding of epithelial dysfunction and the mechanisms underlying intestinal diseases.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2484494"},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of autophagy in ischemic brain injury. 自噬在缺血性脑损伤中的作用。

Autophagy reports Pub Date : 2025-04-03 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2486445

Emily Osterli, Yujung Park, Kurt Hu, Gary Kasof, Thorsten Wiederhold, Chunli Liu, Bingren Hu

{"title":"The role of autophagy in ischemic brain injury.","authors":"Emily Osterli, Yujung Park, Kurt Hu, Gary Kasof, Thorsten Wiederhold, Chunli Liu, Bingren Hu","doi":"10.1080/27694127.2025.2486445","DOIUrl":"10.1080/27694127.2025.2486445","url":null,"abstract":"Ischemic brain injury occurs in many clinical settings, including stroke, cardiac arrest, hypovolemic shock, cardiac surgery, cerebral edema, and cerebral vasospasm. Decades of work have revealed many important mechanisms related to ischemic brain injury. However, there remain significant gaps in the scientific knowledge to reconcile many ischemic brain injury events. Brain ischemia leads to protein misfolding and aggregation, and damages almost all types of subcellular organelles including mitochondria, endoplasmic reticulum, Golgi apparatus, lysosomes, etc. Irreparably damaged organelles and insoluble protein aggregates are normally removed by autophagy. The build-up of common autophagic components, such as LC3, p62, and ubiquitinated proteins, are generally observed in brain tissue samples in animal models of both global and focal brain ischemia, but the interpretation of the role of these autophagy-related changes in ischemic brain injury in the literature has been controversial. Many pathological events or mechanisms underlying dysfunctional autophagy after brain ischemia remain unknown. This review aims to provide an update of the current knowledge and future research directions regarding the critical role of dysfunctional autophagy in ischemic brain injury.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2486445"},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). 自噬在肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTD）的发病机制和治疗中的作用。

Autophagy reports Pub Date : 2025-03-20 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2474796

Jimmy Beckers, Philip Van Damme

{"title":"The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).","authors":"Jimmy Beckers, Philip Van Damme","doi":"10.1080/27694127.2025.2474796","DOIUrl":"10.1080/27694127.2025.2474796","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent two extremes of a neurodegenerative disease spectrum characterised by overlapping genetic, clinical, and neuropathological features. This review covers the intricate relationship between both ALS and FTD and defects in the autophagy and endolysosomal pathway as recent evidence has pointed towards alterations in these pathways as being a root cause of disease pathogenesis. Here, we review the current knowledge on the interplay between ALS/FTD and lysosomebased proteostasis pathways and carefully asses the steps of the autophagy and endolysosomal pathways that are impaired by ALS or FTDcausing variants. Finally, we present a comprehensive overview of therapeutic strategies aimed at restoring autophagic and lysosomal function as potential avenues for mitigating the impact of these devastating diseases. Through this review, we aim to enhance the understanding of the pathophysiological mechanisms involving autophagy and/or the endolysosomal system that underlie the ALS-FTD spectrum and underscore the necessity for specific therapeutic approaches that target these shared vulnerabilities.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2474796"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tropheryma whipplei escapes LAPosome and modulates macrophage response in a xenophagy-dependent manner. 惠氏巨噬瘤逃逸LAPosome并以异种吞噬依赖的方式调节巨噬细胞反应。

Autophagy reports Pub Date : 2025-03-11 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2475527

Emilie Reyne, Jeffrey Arrindell, Eloïne Bestion, Soraya Mezouar, Benoit Desnues

{"title":"Tropheryma whipplei escapes LAPosome and modulates macrophage response in a xenophagy-dependent manner.","authors":"Emilie Reyne, Jeffrey Arrindell, Eloïne Bestion, Soraya Mezouar, Benoit Desnues","doi":"10.1080/27694127.2025.2475527","DOIUrl":"10.1080/27694127.2025.2475527","url":null,"abstract":"Tropheryma whipplei, the agent of Whipple's disease, is an intracellular pathogen that replicates in macrophages. The phagocytic and cellular processes leading to the formation of T. whipplei replicative vacuole remain poorly understood. Macrophage microbicidal activity is largely related to macro/autophagy which is also essential for cell homeostasis. Here, we show that T. whipplei uptake by macrophages involved LC3-associated phagocytosis (LAP). Bacteria then escaped into the cytosol from where they were recaptured by xenophagy. We also demonstrate that T. whipplei blocked the autophagic flux to build its replicative compartment. Inhibition of LAP resulted in the decrease of interleukin (IL)-10 secretion and the restoration of the autophagy flux, suggesting that modulation of autophagy during infection alters immune response and promote persistence. Our results provide new insight in the intracellular fate of the bacteria during macrophage infection and suggest the possible involvement of previously unknown virulence factors in T. whipplei infection.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2475527"},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evidence of the specific roles of autophagy in senescent leaves and maturing seeds. 自噬在衰老叶片和成熟种子中特定作用的证据。

Autophagy reports Pub Date : 2025-03-07 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2472160

Anne Marmagne, Fabien Chardon, Céline Masclaux-Daubresse

{"title":"Evidence of the specific roles of autophagy in senescent leaves and maturing seeds.","authors":"Anne Marmagne, Fabien Chardon, Céline Masclaux-Daubresse","doi":"10.1080/27694127.2025.2472160","DOIUrl":"10.1080/27694127.2025.2472160","url":null,"abstract":"In plants, a large part of the nutrients used to generate seed lipid and protein reserves is derived from both the degradation of macromolecules in source leaves and the transfer of small catabolic molecules like amino acids from the senescing leaves to the seeds. Studies of autophagy mutants in Arabidopsis showed that autophagy is a master player controlling 60% of the remobilization of nitrogen from senescing leaf tissues to developing seeds, and strongly impacting reserve deposition, especially in the protein to lipid ratio. Since autophagy is largely enhanced in leaves during senescence and in the seeds during maturation, we investigated the roles of autophagy in these sources and sink tissues, to identify checkpoints controlling seed filling and quality. Through gene complementation using tissue-specific promoters, we demonstrated that while autophagy regulates nitrogen flux to the seeds in source leaves, the autophagy taking place in seeds during their maturation is essential to reach the appropriate seed quality in terms of C and N storage. Overall, these results highlight the multiple roles of autophagy in the optimal development of the plant throughout its entire lifespan.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2472160"},"PeriodicalIF":0.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Loss of nuclear envelope bud formation leads to mitophagy initiation in Drosophila muscles. 果蝇肌肉核膜芽形成缺失导致有丝分裂起始。

Autophagy reports Pub Date : 2025-03-04 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2471121

Yungui Guo, David Brooks, Ziwei Zhao, Erica Biven, Erika R Geisbrecht

{"title":"Loss of nuclear envelope bud formation leads to mitophagy initiation in Drosophila muscles.","authors":"Yungui Guo, David Brooks, Ziwei Zhao, Erica Biven, Erika R Geisbrecht","doi":"10.1080/27694127.2025.2471121","DOIUrl":"10.1080/27694127.2025.2471121","url":null,"abstract":"Pavarotti (Pav) and its binding partner Tumbleweed (Tum) are well known for their evolutionarily conserved roles in microtubule-dependent movements during cytokinesis. In post-mitotic pav RNAi muscles, we unexpectedly observed the accumulation of puncta marked by ubiquitin, p62, and Atg8a without an obvious disorganization of the microtubule network. Some of these autophagosomal structures clustered together and colocalized with mitochondria. The Pav-Tum complex was enriched in muscle nuclei, consistent with roles for Pav and Tum in nuclear envelope (NE) budding, an alternative pathway for the export of large ribonucleoproteins. One of the established cargoes of the Drosophila NE budding pathway, Marf mRNA, was indeed reduced in the myoplasm of pav RNAi muscles. Moreover, RNAi knockdown of Marf or the NE budding components Wash or Torsin also caused the clustering of p62-marked mitochondria. These data together define a model whereby blocking NE budding reduces mitochondrial activity and in turn recruits p62 and autophagic structures for a lysosomal fate.","PeriodicalId":72341,"journal":{"name":"Autophagy reports","volume":"4 1","pages":"2471121"},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Untangling Traffic Jams: RAB11FIP4 Orchestrates Cellular Recovery in Cystinosis. 解开交通堵塞：RAB11FIP4协调胱氨酸病的细胞恢复。

Autophagy reports Pub Date : 2025-02-19 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2466121

Mouad Ait Kbaich, Jennifer L Johnson, Sergio D Catz

引用次数: 0

Role of neuronal fabp in autophagy and amyloid-β pathology in a Drosophila model of Alzheimer disease. 在阿尔茨海默病果蝇模型中，神经元fabp在自噬和淀粉样蛋白-β病理中的作用。

Autophagy reports Pub Date : 2025-02-13 eCollection Date: 2025-01-01 DOI: 10.1080/27694127.2025.2466120

Byoungyun Choi, Kyoung Sang Cho

引用次数: 0