The Inflammatory Response after Moderate Contusion Spinal Cord Injury: A Time Study DOI Creative Commons
Minna Christiansen Lund,

Ditte Gry Ellman,

Maiken Nissen

et al.

Biology, Journal Year: 2022, Volume and Issue: 11(6), P. 939 - 939

Published: June 20, 2022

Spinal cord injury (SCI) initiates detrimental cellular and molecular events that lead to acute delayed neuroinflammation. Understanding the role of inflammatory response in SCI requires insight into temporal synthesis mediators. We subjected C57BL/6J mice investigated reactions. examined activation, recruitment, polarization microglia infiltrating immune cells, focusing specifically on tumor necrosis factor (TNF) its receptors TNFR1 TNFR2. In phase, TNF expression increased glial cells neuron-like followed by cells. TNFR2 levels phase were found preferentially neurons respectively. The was dominated infiltration granulocytes macrophages. Microglial/macrophage Arg1 from 1-7 days after SCI, an increase Itgam, Cx3cr1, P2ry12, which remained elevated throughout study. By 21 28 lesion core populated galectin-3+, CD68+, CD11b+ microglia/macrophages, surrounded a scar consisting GFAP+ astrocytes. Findings verified postmortem tissue individuals with SCI. Our findings support consensus future neuroprotective immunotherapies should aim selectively neutralize signaling while sustaining pro-regenerative processes.

Language: Английский

Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy DOI Creative Commons
Luca Muzio, Alice Viotti, Gianvito Martino

et al.

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Sept. 24, 2021

Microglia are the resident macrophages of central nervous system (CNS) acting as first line defense in brain by phagocytosing harmful pathogens and cellular debris. emerge from early erythromyeloid progenitors yolk sac enter developing before establishment a fully mature blood–brain barrier. In physiological conditions, during development, microglia contribute to CNS homeostasis supporting cell proliferation neural precursors. post-natal life, such cells preserving integrity neuronal circuits sculpting synapses. After injury, change their morphology down-regulate those genes homeostatic functions. However, it is still unclear whether changes accompanied molecular functional modifications that might pathological process. While comprehensive transcriptome analyses at single-cell level have identified specific gene perturbations occurring “pathological” microglia, precise protective/detrimental role neurological disorders far being elucidated. this review, results so obtained regarding neurodegenerative will be discussed. There solid sound evidence suggesting regulating functions disease pathology represent strategy develop future therapies aimed counteracting degeneration multiple sclerosis, Alzheimer’s disease, Parkinson’s amyotrophic lateral sclerosis.

Language: Английский

Citations

358
Injured sensory neurons-derived galectin-3 contributes to neuropathic pain via programming microglia in the spinal dorsal horn DOI

Leyan Shan,

Kangtai Xu,

Luyao Ji

et al.

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 117, P. 80 - 99

Published: Jan. 6, 2024

Language: Английский

Citations

17
Novel Galectin-3 Roles in Neurogenesis, Inflammation and Neurological Diseases DOI Creative Commons
Luana Campos Soares, Osama Al‐Dalahmah, James Hillis

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 3047 - 3047

Published: Nov. 5, 2021

Galectin-3 (Gal-3) is an evolutionarily conserved and multifunctional protein that drives inflammation in disease. Gal-3’s role the central nervous system has been less studied than immune system. However, recent studies show it exacerbates Alzheimer’s disease upregulated a large variety of brain injuries, while loss Gal-3 function can diminish symptoms neurodegenerative diseases such as Alzheimer’s. Several novel molecular pathways for were recently uncovered. It natural ligand TREM2 (triggering receptor expressed on myeloid cells), TLR4 (Toll-like 4), IR (insulin receptor). regulates number including stimulation bone morphogenetic (BMP) signaling modulating Wnt signalling context-dependent manner. typically acts pathology but now known to affect subventricular zone (SVZ) neurogenesis gliogenesis healthy brain. Despite its myriad interactors, surprisingly specific important functions regulating SVZ Gal-1, similar lectin often co-expressed with Gal-3, also profound effects adult neurogenesis. Remarkably, carbohydrate recognition domain bears structural similarity SARS-CoV-2 virus spike necessary cell entry. be targeted pharmacologically valid target several involving inflammation. The wealth further suggest modulation could therapeutically useful.

Language: Английский

Citations

64
Microglia dynamics in aging-related neurobehavioral and neuroinflammatory diseases DOI Creative Commons

Nima Javanmehr,

Kiarash Saleki,

Parsa Alijanizadeh

et al.

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: Nov. 17, 2022

Abstract Microglia represent the first line of immune feedback in brain. Beyond surveillance, they are essential for maintaining brain homeostasis. Recent research has revealed microglial cells' spatiotemporal heterogeneity based on their local and time-based functions trauma or disease when homeostasis is disrupted. Distinct "microglial signatures" have been recorded physiological states injuries, with discrete sometimes overlapping pro- anti-inflammatory functions. involved neurological repair processes, such as neurovascular unit restoration synaptic plasticity, manage extent damage due to phenotype switching. The versatility cellular phenotypes beyond classical M1/M2 classification, well double-edge actions microglia neurodegeneration, indicate need further exploration cell dynamics contribution neurodegenerative processes. This review discusses homeostatic different subsets focusing neuropathological conditions. Also, we address feasibility targeting a therapeutic strategy diseases.

Language: Английский

Citations

60
Emerging roles of astrocytes in blood-brain barrier disruption upon amyloid-beta insults in Alzheimer's disease DOI Creative Commons

MaggiePui Man Hoi,

Qian Yue

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 0(0), P. 0 - 0

Published: Jan. 1, 2023

Blood-brain barrier disruption occurs in the early stages of Alzheimer's disease. Recent studies indicate a link between blood-brain dysfunction and cognitive decline might accelerate disease progression. Astrocytes are most abundant glial cells central nervous system with important roles structural functional maintenance barrier. For example, astrocytic coverage around endothelial perivascular endfeet secretion homeostatic soluble factors two major underlying mechanisms physiological functions. Astrocyte activation is often observed patients, astrocytes expressing high level fibrillary acid protein detected amyloid-beta plaque elevated phagocytic ability for amyloid-beta. Structural alterations including swollen endfeet, somata shrinkage possess loss contribute to vascular integrity at capillary arterioles levels. In addition, skewed into proinflammatory oxidative profiles increased secretions vasoactive mediators inducing junction immune cell infiltration. this review, we summarize findings existing literature on relevance astrocyte alteration response amyloid pathology context dysfunction. First, briefly describe maintenance. Then, review clinical evidence patients preclinical animal cellular models. We further discuss changes that correlates astrocyte. Finally, evaluate secreted by astrocytes, providing potential molecular modulation. conclude perspective investigating therapeutic targeting protection

Language: Английский

Citations

39
Elevated Galectin-3 Is Associated with Aging, Multiple Sclerosis, and Oxidized Phosphatidylcholine-Induced Neurodegeneration DOI Creative Commons

Sara Xue,

Brian M. Lozinski, Samira Ghorbani

et al.

Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 43(25), P. 4725 - 4737

Published: May 19, 2023

Aging is a significant risk factor associated with the progression of CNS neurodegenerative diseases including multiple sclerosis (MS). Microglia, resident macrophages parenchyma, are major population immune cells that accumulate in MS lesions. While they normally regulate tissue homeostasis and facilitate clearance neurotoxic molecules oxidized phosphatidylcholines (OxPCs), their transcriptome neuroprotective functions reprogrammed by aging. Thus, determining factors instigate aging microglia dysfunction can lead to new insights for promoting repair halting disease progression. Through single-cell RNA sequencing (scRNAseq), we identified Lgals3, which encodes galectin-3 (Gal3), as an age upregulated gene responding OxPC. Consistently, excess Gal3 accumulated OxPC lysolecithin-induced focal spinal cord white matter (SCWM) lesions middle-aged mice compared young mice. was also elevated mouse experimental autoimmune encephalomyelitis (EAE) more importantly brain from two male one female individuals. delivery alone into did not induce damage, its co-delivery increased cleaved caspase 3 IL-1β within exacerbated OxPC-induced injury. Conversely, OxPC-mediated neurodegeneration reduced Gal3-/- Gal3+/+ neuroinflammation overexpression microglia/macrophages may be detrimental CNS.SIGNIFICANCE STATEMENT accelerates such Understanding molecular mechanisms increases susceptibility damage could strategies manage Here, highlight microglia/macrophage-associated (Gal3) More importantly, co-injection lipids found lesions, caused greater injection alone, whereas genetic loss damage. These results demonstrate suggest deposition contribute neurodegeneration.

Language: Английский

Citations

23
Synaptic plasticity and neuroprotection: The molecular impact of flavonoids on neurodegenerative disease progression DOI

Spandana Rajendra Kopalli,

Tapan Behl,

Ashishkumar Kyada

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: 569, P. 161 - 183

Published: Feb. 7, 2025

Language: Английский

Citations

1
Ai-Driven Discovery of Brain-Penetrant Galectin-3 Inhibitors for Alzheimer's Disease Therapy DOI
Zu‐Cheng Ye, Xueyan Liu,

Jiexin Xu

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

1
The Role of Microglia in the Development of Neurodegenerative Diseases DOI Creative Commons
Jae‐Won Lee, Wanjoo Chun, Hee Jae Lee

et al.

Biomedicines, Journal Year: 2021, Volume and Issue: 9(10), P. 1449 - 1449

Published: Oct. 12, 2021

Microglia play an important role in the maintenance and neuroprotection of central nervous system (CNS) by removing pathogens, damaged neurons, plaques. Recent observations emphasize that promotion development neurodegenerative diseases (NDs) are closely related to microglial activation. In this review, we summarize contribution activation its associated mechanisms NDs, such as epilepsy, Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), based on recent observations. This review also briefly introduces experimental animal models AD, PD, HD. Thus, provides a better understanding functions suggesting targeting could be effective therapeutic strategy for these diseases.

Language: Английский

Citations

42
LGALS3 (galectin 3) mediates an unconventional secretion of SNCA/α-synuclein in response to lysosomal membrane damage by the autophagic-lysosomal pathway in human midbrain dopamine neurons DOI Creative Commons
Kevin Burbidge,

David J. Rademacher,

Jessica Mattick

et al.

Autophagy, Journal Year: 2021, Volume and Issue: 18(5), P. 1020 - 1048

Published: Oct. 6, 2021

Numerous lines of evidence support the premise that misfolding and subsequent accumulation SNCA/α-synuclein (synuclein alpha) is responsible for underlying neuronal pathology observed in Parkinson disease (PD) other synucleinopathies. Moreover, cell-to-cell transfer these misfolded SNCA species thought to be progression spread cellular throughout brain. Previous work has shown when exogenous, fibrils enter cells through endocytosis, they can damage rupture membranes their endocytotic vesicles which are trafficked. Rupture vesicular exposes intralumenal glycans leading galectin protein binding, autophagic recruitment, and, ultimately, introduction into autophagic-lysosomal pathway. Increasing indicates both pathological non-pathological undergo autophagy-dependent unconventional secretion. While proteins have also been secreted from by autophagy, what triggers this release process how specific recruited a secretory pathway largely unknown. Here, we use human midbrain dopamine (mDA) culture model provide mechanism explains forms PD. We demonstrate LGALS3 (galectin 3) mediates following damage. dependent on TRIM16 (tripartite motif containing 16) ATG16L1 (autophagy related 16 like 1), providing secretion mediated an

Language: Английский

Citations

41