Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth DOI Creative Commons

Luis Cruz Hernández,

María Teresa Sánchez Montero,

Alberto Rivera-Ramos

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 15, 2023

ABSTRACT The glycoprotein Galectin-3 (Gal-3) is a multifunctional molecule that plays pivotal role in the initiation and progression of various central nervous system diseases, including cancer. Although involvement Gal-3 tumour progression, resistance to treatment immunosuppression has long been studied different cancer types, mainly outside system, its elevated expression myeloid glial cells underscores profound impact on brain’s immune response. In this context, microglia infiltrating macrophages, predominant non-cancerous within microenvironment, assume critical roles establishing an immunosuppressive milieu diverse brain tumours. Through utilisation primary cell cultures immortalised microglial lines, we have elucidated promoting migration, invasion, phenotypic activation. Furthermore, employing two distinct vivo models encompassing (glioblastoma) secondary tumours (breast metastasis), our histological transcriptomic analysis show depletion triggers robust pro-inflammatory response notably based interferon-related pathways. Interestingly, prominently observed tumour-associated macrophages (TAMs), resulting suppression growth.

Language: Английский

Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth DOI Creative Commons
Alberto Rivera-Ramos, Luis Cruz-Hernández, Rocío Talaverón

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 591, P. 216879 - 216879

Published: April 16, 2024

Galectin-3 (Gal-3) is a multifunctional protein that plays pivotal role in the initiation and progression of various central nervous system diseases, including cancer. Although involvement Gal-3 tumour progression, resistance to treatment immunosuppression has long been studied different cancer types, mainly outside system, its elevated expression myeloid glial cells underscores profound impact on brain's immune response. In this context, microglia infiltrating macrophages, predominant non-cancerous within microenvironment, play critical roles establishing an immunosuppressive milieu diverse brain tumours. Through utilisation primary cell cultures immortalised microglial lines, we have elucidated promoting migration, invasion, phenotypic activation. Furthermore, employing two distinct vivo models encompassing (glioblastoma) secondary tumours (breast metastasis), our histological transcriptomic analysis show depletion triggers robust pro-inflammatory response notably based interferon-related pathways. Interestingly, prominently observed tumour-associated macrophages (TAMs), resulting suppression growth.

Language: Английский

Citations

4
Mapping dynamic molecular changes in hippocampal subregions after traumatic brain injury through spatial proteomics DOI Creative Commons
Sudipa Maity, Yuanyu Huang, Mitchell D. Kilgore

et al.

Clinical Proteomics, Journal Year: 2024, Volume and Issue: 21(1)

Published: May 12, 2024

Abstract Background Traumatic brain injury (TBI) often results in diverse molecular responses, challenging traditional proteomic studies that measure average changes at tissue levels and fail to capture the complexity heterogeneity of affected tissues. Spatial proteomics offers a solution by providing insights into sub-region-specific alterations within This study focuses on hippocampal sub-regions, analyzing expression profiles mice acute (1 day) subacute (7 days) phases post-TBI understand subregion-specific vulnerabilities long-term consequences. Methods Three brains were collected from each group, including Sham, 1-day 7-day post-TBI. Hippocampal subregions extracted using Laser Microdissection (LMD) subsequently analyzed label-free quantitative proteomics. Results The spatial analysis reveals region-specific protein abundance changes, highlighting elevation FN1, LGALS3BP, HP, MUG-1 stratum moleculare (SM), suggesting potential immune cell enrichment Notably, established markers chronic traumatic encephalopathy, IGHM B2M, exhibit specific upregulation dentate gyrus bottom (DG2) independent direct mechanical injury. Metabolic pathway identifies disturbances glucose lipid metabolism, coupled with activated cholesterol synthesis pathways enriched SM 7-Day deeper DG1 DG2 role neurogenesis onset recovery. Coordinated activation neuroglia microtubule dynamics suggest recovery mechanisms less regions. Cluster revealed variations post-TBI, indicative dysregulated neuronal plasticity further predisposition neurological disorders. TBI-induced (MUG-1, PZP, GFAP, TJP, STAT-1, CD44) across sub-regions indicates shared responses links demonstrated proteins both or either time-points exclusively subregion (ELAVL2, CLIC1 PL, CD44 SM, SHOC2, LGALS3 DG). Conclusions Utilizing advanced techniques, unveils dynamic distinct It uncovers processes, recovery-related contribute our understanding TBI’s consequences provides valuable for biomarker discovery therapeutic targets.

Language: Английский

Citations

4
Lysosome quality control in health and neurodegenerative diseases DOI Creative Commons
Veronica Ferrari, B. Tedesco, Marta Cozzi

et al.

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: Sept. 5, 2024

Abstract Lysosomes are acidic organelles involved in crucial intracellular functions, including the degradation of and protein, membrane repair, phagocytosis, endocytosis, nutrient sensing. Given these key roles lysosomes, maintaining their homeostasis is essential for cell viability. Thus, to preserve lysosome integrity functionality, cells have developed a complex system, called quality control (LQC). Several stressors may affect causing Lysosomal permeabilization (LMP), which rupture results leakage luminal hydrolase enzymes into cytosol. After sensing damage, LQC either activates or induces ruptured lysosomes through autophagy. In addition, stimulates de novo biogenesis functional exocytosis. Alterations give rise deleterious consequences cellular homeostasis. Specifically, persistence impaired malfunctioning lysosomal processes leads toxicity death, thereby contributing pathogenesis different disorders, neurodegenerative diseases (NDs). Recently, several pieces evidence underlined importance role NDs. this review, we describe elements how they cooperate maintain homeostasis, implication Graphical

Language: Английский

Citations

4
Plasma galectin-3 can be considered as a non-invasive marker to predict the prognosis of ACLF patients with new typing DOI Creative Commons
Bai Li, Lu Wang, Huazhe Yang

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 31, 2025

Very recently, we creatively put forward a new classification for ACLF patients, which lays the foundation establishment of prognostic model that can accurately predict prognosis patients. Herein, found: galectin-3 levels were higher in type A patients compared to those B patients; expression was closely correlated with TBil, PTA/INR and MELD; is an independent predictive factor rapid progression ACLF, exhibited superior value than MELD score; survival rate remarkably lower expression. Collectively, be considered as non-invasive biomarker typing. Our findings help advance time window prediction from 4 weeks baseline, thereby identifying who really need liver transplantation earlier improving

Language: Английский

Citations

0
Identification of age-related metabolomic signatures in vascular tissues DOI

Ya Li Zhao,

Jingyue Zhang,

Jiao Xia

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: 754, P. 151513 - 151513

Published: Feb. 19, 2025

Language: Английский

Citations

0
The role of microglia in the prion-like transmission of protein aggregates in neurodegeneration DOI Creative Commons
Masum Öztürk,

Jakob Emgård,

Juan García‐Revilla

et al.

Brain Communications, Journal Year: 2025, Volume and Issue: 7(2)

Published: Jan. 1, 2025

Numerous neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis share a neuropathological hallmark: aberrant protein aggregation in the CNS. Microglia, brain's innate immune cells, also play pivotal role pathogenesis of these disorders. Multiple studies indicate that pathological aggregates can propagate throughout brain prion-like manner. A protein/peptide adopts conformation induce homologous proteins to misfold into through templated seeding, enabling cell-to-cell spread accelerating brain. Two important questions paradigm are where misfolding occurs how Here, we review microglia associated inflammation pathologically aggregated proteins/peptides sclerosis. growing body evidence suggests internalize transport them neighbouring neurons other glial cells. Microglia may influence potential seeding inflammatory pathways their microenvironment. This aims broaden understanding aggregation.

Language: Английский

Citations

0
Novel strategies in Parkinson’s disease treatment: a review DOI Creative Commons

Charles L. Mitchell,

Dmitry Kurouski

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Aug. 9, 2024

An unprecedented extension of life expectancy observed during the past century drastically increased number patients diagnosed with Parkinson’s diseases (PD) worldwide. Estimated costs PD alone reached $52 billion per year, making effective neuroprotective treatments an urgent and unmet need. Current both AD focus on mitigating symptoms associated these pathologies are not neuroprotective. In this review, we discuss most advanced therapeutic strategies that can be used to treat PD. We also critically review shift paradigm from a small molecule-based inhibition protein aggregation utilization natural degradation pathways immune cells capable degrading toxic amyloid deposits in brain patients.

Language: Английский

Citations

3
Multiomics approach identifies dysregulated lipidomic and proteomic networks in Parkinson’s disease patients mutated in TMEM175 DOI Creative Commons
Federica Carrillo, Marco Ghirimoldi, Giorgio Fortunato

et al.

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 24, 2025

Language: Английский

Citations

0
Galectin‐3 is upregulated in frontotemporal dementia patients with subtype specificity DOI Creative Commons
Sergi Borrego‐Écija, Agnès Pérez‐Millan, Anna Antonell

et al.

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 20(3), P. 1515 - 1526

Published: Nov. 29, 2023

Abstract INTRODUCTION Neuroinflammation is a major contributor to the progression of frontotemporal dementia (FTD). Galectin‐3 (Gal‐3), microglial activation regulator, holds promise as therapeutic target and potential biomarker. Our study aimed investigate Gal‐3 levels in patients with FTD assess its diagnostic potential. METHODS We examined brain, serum, cerebrospinal fluid (CSF) samples controls. Multiple linear regressions between other markers were explored. RESULTS increased significantly FTD, mainly across brain tissue CSF, compared Remarkably, higher cases tau pathology than TAR‐DNA Binding Protein 43 (TDP‐43) pathology. Only MAPT mutation carriers displayed CSF samples, which correlated total 14‐3‐3. DISCUSSION findings underscore marker for particularly cases, highlights relation neuronal injury markers.

Language: Английский

Citations

8
Emerging role of galectin 3 in neuroinflammation and neurodegeneration DOI Creative Commons
Brian M. Lozinski,

Khanh Ta,

Yifei Dong

et al.

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(9), P. 2004 - 2009

Published: Dec. 21, 2023

Neuroinflammation and neurodegeneration are key processes that mediate the development progression of neurological diseases. However, mechanisms modulating these in different diseases remain incompletely understood. Advances single cell based multi-omic analyses have helped to identify distinct molecular signatures such as Lgals3 is associated with neuroinflammation central nervous system (CNS). encodes galectin-3 (Gal3), a β-galactoside glycan binding glycoprotein frequently upregulated by reactive microglia/macrophages CNS during various While Gal3 has previously been non-CNS inflammatory fibrotic diseases, recent studies highlight prominent regulator inflammation neuroaxonal damage multiple sclerosis, Alzheimer's disease, Parkinson's disease. In this review, we summarize pleiotropic functions discuss evidence demonstrates its detrimental role We also consider challenges translating preclinical observations into targeting human CNS.

Language: Английский

Citations

8