Alpha Synuclein: Neurodegeneration and Inflammation

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5914 - 5914

Published: March 21, 2023

Alpha-Synuclein (α-Syn) is one of the most important molecules involved in pathogenesis Parkinson’s disease and related disorders, synucleinopathies, but also several other neurodegenerative disorders with a more elusive role. This review analyzes activities α-Syn, different conformational states, monomeric, oligomeric fibrils, relation to neuronal dysfunction. The damage induced by α-Syn various conformers will be analyzed its capacity spread intracellular aggregation seeds prion-like mechanism. In view prominent role inflammation virtually all activity illustrated considering influence on glial reactivity. We others have described interaction between general cerebral dysfunctional α-Syn. Differences microglia astrocyte activation been observed when vivo presence oligomers has combined lasting peripheral inflammatory effect. reactivity was amplified, while astrocytes were damaged double stimulus, opening new perspectives for control synucleinopathies. Starting from our studies experimental models, we extended perspective find useful pointers orient future research potential therapeutic strategies disorders.

Language: Английский

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Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 15(1), P. 15 - 34

Published: Oct. 16, 2024

Neuroprotection is a proactive approach to safeguarding the nervous system, including brain, spinal cord, and peripheral nerves, by preventing or limiting damage nerve cells other components. It primarily defends central system against injury from acute progressive neurodegenerative disorders. Oxidative stress, an imbalance between body's natural defense mechanisms generation of reactive oxygen species, crucial in developing neurological Due its high metabolic rate consumption, brain particularly vulnerable oxidative stress. Excessive ROS damages essential biomolecules, leading cellular malfunction neurodegeneration. Several disorders, Alzheimer's, Parkinson's, Amyotrophic lateral sclerosis, multiple ischemic stroke, are associated with Understanding impact stress these conditions for new treatment methods. Researchers exploring using antioxidants molecules mitigate aiming prevent slow down progression diseases. By understanding intricate interplay scientists hope pave way innovative therapeutic preventive approaches, ultimately improving individuals' living standards.

Language: Английский

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Polyethylene microplastics induced gut microbiota dysbiosis leading to liver injury via the TLR2/NF-κB/NLRP3 pathway in mice

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 917, P. 170518 - 170518

Published: Jan. 28, 2024

Language: Английский

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Toll‐like receptors in pathogenesis of neurodegenerative diseases and their therapeutic potential

Immunity Inflammation and Disease, Journal Year: 2023, Volume and Issue: 11(4)

Published: April 1, 2023

Abstract Toll‐like receptors (TLRs) are a family of pattern‐recognition triggered by pathogen‐derived and tissue‐damage‐related ligands. TLRs were previously believed to only be expressed in immune cells. However, it is now confirmed that they ubiquitously cells within the body including neurons, astrocytes, microglia central nervous system (CNS). Activation capable inducing immunologic inflammatory responses injury or infection CNS. This response self‐limiting usually resolves once has been eradicated tissue damage repaired. persistence inflammation‐inducing insults failure normal resolution mechanisms may result overwhelming inflammation which induce neurodegeneration. implies play role mediating link between neurodegenerative diseases namely Alzheimer's disease, Parkinson's Huntington's stroke, amyotrophic lateral sclerosis. So, new therapeutic approaches specifically target developed better understanding TLR expression CNS their connections particular disorders. Therefore, this review paper discussed diseases.

Language: Английский

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SOCS modulates JAK-STAT pathway as a novel target to mediate the occurrence of neuroinflammation: Molecular details and treatment options

Brain Research Bulletin, Journal Year: 2024, Volume and Issue: 213, P. 110988 - 110988

Published: May 27, 2024

SOCS (Suppressor of Cytokine Signalling) proteins are intracellular negative regulators that primarily modulate and inhibit cytokine-mediated signal transduction, playing a crucial role in immune homeostasis related inflammatory diseases. act as inhibitors by regulating the Janus kinase-signal transducer activator transcription (JAK-STAT) signaling pathway, thereby intervening pathogenesis inflammation autoimmune Recent studies have also demonstrated their involvement central immunity neuroinflammation, showing dual functionality. However, specific mechanisms nervous system remain unclear. This review thoroughly elucidates linking SOCS-JAK-STAT pathway with manifestations neurodegenerative Based on this, it proposes theory can regulate JAK-STAT occurrence neuroinflammation. Additionally, this explores detail current therapeutic landscape potential targeting brain via for offering insights into targets treatment

Language: Английский

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Microglial NLRP3 inflammasome-mediated neuroinflammation and therapeutic strategies in depression

Neural Regeneration Research, Journal Year: 2023, Volume and Issue: 19(9), P. 1890 - 1898

Published: Dec. 14, 2023

Previous studies have demonstrated a bidirectional relationship between inflammation and depression. Activation of the nucleotide-binding oligomerization domain, leucine-rich repeat, NLR family pyrin domain-containing 3 (NLRP3) inflammasomes is closely related to pathogenesis various neurological diseases. In patients with major depressive disorder, NLRP3 inflammasome levels are significantly elevated. Understanding role that inflammasome-mediated neuroinflammation plays in depression may be beneficial for future therapeutic strategies. this review, we aimed elucidate mechanisms lead activation as well provide insight into strategies target inflammasome. Moreover, outlined inflammasome, including inflammatory pathway inhibitors, natural compounds, other compounds been shown effective treating Additionally, summarized application inhibitors clinical trials Currently, there scarcity dedicated investigating applications treatment. The modulation microglia holds promise management Further investigations necessary ascertain efficacy safety these approaches potential novel antidepressant treatments.

Language: Английский

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Program with last minute abstracts of the Padua Days on Muscle and Mobility Medicine, 27 February – 2 March, 2024 (2024Pdm3)

European Journal of Translational Myology, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 2, 2024

During the 2023 Padua Days on Muscle and Mobility Medicine 2024 meeting was scheduled from 28 February to 2 March (2024Pdm3). autumn program expanded with Scientific Sessions which will take place over five days (in this includes 29), starting afternoon of 27 in Conference Rooms Hotel Petrarca, Thermae Euganean Hills (Padua), Italy. As per consolidated tradition, second day Padua, for occasion Sala San Luca Monastery Santa Giustina Prato della Valle, Confirming attractiveness Medicine, 100 titles were accepted until 15 December (many more than expected), forcing organization parallel sessions both 1 2024. The include lectures oral presentations scientists clinicians Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Denmark, Egypt, France, Germany, Iceland, Ireland, Italy, Romania, Russia, Slovenia, Switzerland, UK USA. Only Australia, China, India Japan are missing edition. But we confident that authors those countries who publish articles PAGEpress: European Journal Translational Myology (EJTM: 2022 ESCI Clarivate's Impact Factor: 2.2; SCOPUS Cite Score: 3.2) decide join us coming years. Together established by 31 January 2024, abstracts circulate during only electronic version EJTM Issue 34 (1) See you soon person at Petrarca Montegrotto Terme, inauguration or on-line free via Zoom. Send your email address if not traditional participants listed Pdm3 books.

Language: Английский

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Mitochondrial Dysfunction is a Crucial Immune Checkpoint for Neuroinflammation and Neurodegeneration: mtDAMPs in Focus

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 8, 2024

Language: Английский

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Glial cells improve Parkinson’s disease by modulating neuronal function and regulating neuronal ferroptosis

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 3, 2025

The main characteristics of Parkinson's disease (PD) are the loss dopaminergic (DA) neurons and abnormal aggregation cytosolic proteins. However, exact pathogenesis PD remains unclear, with ferroptosis emerging as one key factors driven by iron accumulation lipid peroxidation. Glial cells, including microglia, astrocytes, oligodendrocytes, serve supportive cells in central nervous system (CNS), but their activation can lead to DA neuron death ferroptosis. This paper explores interactions between glial neurons, reviews changes during pathological process PD, reports on how regulate through homeostasis opens up a new pathway for basic research therapeutic strategies disease.

Language: Английский

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Helicobacter pylori infection promotes M1 macrophage polarization and gastric inflammation by activation of NLRP3 inflammasome via TNF/TNFR1 axis

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 6, 2025

Macrophages play a crucial role in chronic gastritis induced by the pathogenic Helicobacter pylori (H. pylori) infection. NLRP3 inflammasome has emerged as an important component of inflammatory processes. However, molecular mechanism which H. infection drives and macrophages activation remains unclear. Human tissues were collected for clinical significance NLRP3. Infection with was performed using vitro vivo models. Bone marrow-derived (BMDMs) from wild-type (WT), Nlrp3-knockout (KO) Tnfr1-KO mice infected pylori. Western blotting, qRT-PCR, immunofluorescence, immunohistochemistry ELISA utilized functional mechanistic studies. Single-cell RNA sequencing (ScRNA-seq) analysis human gastric tissues, followed validation, indicated that primarily expressed myeloid cells significantly increased pylori-positive compared to pylori-negative gastritis. PMSS1 NCTC11637 strains (THP1 cells) insulin-gastrin (INS-GAS) transgenic mouse model. Deletion BMDMs showed marked inhibition pylori-induced M1 macrophage polarization. Furthermore, upon TNFα, or stimulation, partially blocked TNFα/TNFR1 signaling inhibitors. TNFR1 impaired This study revealed inflammasome, regulated TNF/TNFR1 axis, is key regulator

Language: Английский

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