Modulation of the immunity and inflammation by autophagy DOI Creative Commons
Ting Gan,

Shu Qu,

Hong Zhang

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(4)

Published: July 2, 2023

Abstract Autophagy, a highly conserved cellular self‐degradation pathway, has emerged with novel roles in the realms of immunity and inflammation. Genome‐wide association studies have unveiled correlation between genetic variations autophagy‐related genes heightened susceptibility to autoimmune inflammatory diseases. Subsequently, substantial progress been made unraveling intricate involvement autophagy inflammation through functional studies. The pathway plays crucial role both innate adaptive immunity, encompassing various key functions such as pathogen clearance, antigen processing presentation, cytokine production, lymphocyte differentiation survival. Recent research identified approaches which its associated proteins modulate immune response, including noncanonical autophagy. This review provides an overview latest advancements understanding regulation It summarizes associations variants range diseases, while also examining utilizing transgenic animal models uncover vivo Furthermore, delves into mechanisms by dysregulation contributes development three common diseases highlights potential for autophagy‐targeted therapies.

Language: Английский

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

1
The autophagy component LC3 regulates lymphocyte adhesion via LFA1 transport in response to outside-in signaling DOI Creative Commons
N Kondo, Yuko Mimori‐Kiyosue, Keizo Tokuhiro

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 4, 2025

The leukocyte integrin LFA1 is indispensable for immune responses, orchestrating lymphocyte trafficking and adhesion. While activation induces clustering at the cell contact surface via outside-in signaling, regulatory mechanisms remain unclear. Here, we uncovered a previously hidden function of autophagosome component LC3 beyond its role in autophagy by bridging two seemingly unrelated pathways: transport transport. clusters co-trafficked with LC3, facilitating accumulation surface. LC3b knockout decreased adhesiveness. did not induce autophagy, whereas it increased mTOR AMPK activity. LFA1-dependent enhances Inhibiting Mst1 kinase-mediated phosphorylation promoted LC3-mediated recruitment to through direct interaction RAPL, uncovering an unprecedented route. These findings uncover expand our understanding regulation LFA1. required canonical non-canonical autophagy. authors LAPTIN, triggered which activates drive co-clustering thereby increasing

Language: Английский

Citations

1
Profiling of purified autophagic vesicle degradome in the maturing and aging brain DOI Creative Commons

Emmanouela Kallergi,

Devanarayanan Siva Sankar,

A. Matera

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(15), P. 2329 - 2347.e7

Published: June 5, 2023

Autophagy disorders prominently affect the brain, entailing neurodevelopmental and neurodegenerative phenotypes in adolescence or aging, respectively. Synaptic behavioral deficits are largely recapitulated mouse models with ablation of autophagy genes brain cells. Yet, nature temporal dynamics autophagic substrates remain insufficiently characterized. Here, we immunopurified LC3-positive vesicles (LC3-pAVs) from proteomically profiled their content. Moreover, characterized LC3-pAV content that accumulates after macroautophagy impairment, validating a degradome. We reveal selective pathways for aggrephagy, mitophagy, ER-phagy via receptors, turnover numerous synaptic substrates, under basal conditions. To gain insight into protein turnover, quantitatively compared adolescent, adult, aged brains, revealing critical periods enhanced mitophagy degradation substrates. Overall, this resource unbiasedly characterizes contribution to proteostasis maturing, brain.

Language: Английский

Citations

22
Autophagy deficiency protects against ocular hypertension and neurodegeneration in experimental and spontaneous glaucoma mouse models DOI Creative Commons
Angela Dixon, Myoung Sup Shim, April Nettesheim

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(8)

Published: Aug. 24, 2023

Abstract Glaucoma is a group of diseases that leads to chronic degeneration retinal ganglion cell (RGC) axons and progressive loss RGCs, resulting in vision loss. While aging elevated intraocular pressure (IOP) have been identified as the main contributing factors glaucoma, molecular mechanisms signaling pathways triggering RGC death axonal are not fully understood. Previous studies our laboratory found overactivation autophagy DBA/2J::GFP-LC3 mice led optic nerve with glaucomatous IOP elevation. We similar findings GFP-LC3 subjected Here, we further investigated impact deficiency on autophagy-deficient DBA/2J- Atg4b ko +/− mice, generated via CRISPR/Cas9 technology; well experimental TGFβ2 ocular hypertensive model. Our data shows that, contrast DBA/2J littermates, do develop also protected against elevation Atg4 deletion did compromise or survival mice. Moreover, results indicate protective role ON atrophy Together, suggests pathogenic activation hypertension glaucoma.

Language: Английский

Citations

18
LC3-associated phagocytosis promotes glial degradation of axon debris after injury in Drosophila models DOI Creative Commons
Áron Szabó,

Virág Vincze,

Aishwarya Chhatre

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 29, 2023

Glial engulfment of neuron-derived debris after trauma, during development, and in neurodegenerative diseases supports nervous system functions. However, mechanisms governing the efficiency degradation glia have remained largely unexplored. Here we show that LC3-associated phagocytosis (LAP), an pathway assisted by certain autophagy factors, promotes glial phagosome maturation Drosophila wing nerve. A LAP-specific subset autophagy-related genes is required for axon clearance, encoding members Atg8a (LC3) conjugation Vps34 lipid kinase complex including UVRAG Rubicon. Phagosomal Rubicon Atg16 WD40 domain-dependent mediate proper breakdown internalized fragments, overexpression accelerates elimination. Finally, LAP survival following traumatic brain injury. Our results reveal a role clearance neuronal vivo, with potential implications recovery injured system.

Language: Английский

Citations

17
Cinnamaldehyde Alleviates Aspirin-Induced Gastric Mucosal Injury by regulating PI3K/AKT Pathway-Mediated Apoptosis, Autophagy, and Ferroptosis DOI Creative Commons

Shuguang Yan,

Shengchuan Bao,

Ting Chen

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 132, P. 155791 - 155791

Published: May 29, 2024

Gastric mucosal injury is a chronic and progressive stomach disease that can be caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, there an urgent need to find safe effective prevent gastric due NSAIDs. Cinnamaldehyde (CA) bioactive compound extracted from the rhizome of cinnamon has various pharmacological functions, including anti-inflammatory, analgesic, antiapoptotic, antioxidant activities. However, potential effect CA on remains unknown.

Language: Английский

Citations

7
EDIL3/Del-1 prevents aortic dissection through enhancing internalization and degradation of apoptotic vascular smooth muscle cells DOI
Zheng Yin, Jishou Zhang, Mengmeng Zhao

et al.

Autophagy, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 21

Published: June 14, 2024

Thoracic aortic dissection (TAD) is a severe disease, characterized by numerous apoptotic vascular smooth muscle cells (VSMCs). EDIL3/Del-1 secreted protein involved in macrophage efferocytosis acute inflammation. Here, we aimed to investigate whether EDIL3 promoted the internalization and degradation of VSMCs during TAD. The levels were decreased serum tissue from TAD mice. Global

Language: Английский

Citations

7
Quercetin activates autophagy to protect rats ovarian granulosa cells from H2O2-induced aging and injury DOI
Minghui Cai, Qiuyuan Li, Yang Cao

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 966, P. 176339 - 176339

Published: Jan. 23, 2024

Language: Английский

Citations

6
Sonicated polyethylene terephthalate nano- and micro-plastic-induced inflammation, oxidative stress, and autophagy in vitro DOI
Walison Augusto da Silva Brito, Mehdi Ravandeh,

Fariba Saadati

et al.

Chemosphere, Journal Year: 2024, Volume and Issue: 355, P. 141813 - 141813

Published: April 3, 2024

Language: Английский

Citations

6
Manipulation of host phagocytosis by fungal pathogens and therapeutic opportunities DOI
Lei‐Jie Jia, Katherine González, Thomas Orasch

et al.

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(9), P. 2216 - 2231

Published: Aug. 26, 2024

Language: Английский

Citations

6