Multiple Sclerosis: Inflammatory and Neuroglial Aspects

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(2), P. 1443 - 1470

Published: Feb. 8, 2023

Multiple sclerosis (MS) represents the most common acquired demyelinating disorder of central nervous system (CNS). Its pathogenesis, in parallel with well-established role mechanisms pertaining to autoimmunity, involves several key functions immune, glial and nerve cells. The disease’s natural history is complex, heterogeneous may evolve over a relapsing-remitting (RRMS) or progressive (PPMS/SPMS) course. Acute inflammation, driven by infiltration peripheral cells CNS, thought be relevant process during earliest phases RRMS, while disruption neural pathways energy metabolism, survival cascades, synaptic ionic homeostasis are mostly long-standing disease, such as forms. In this complex scenario, many originally distinctive neurodegenerative disorders being increasingly recognized crucial from beginning disease. present review aims at highlighting between MS, autoimmune diseases biology disorders. fact, there an unmet need explore new targets that might involved master regulators inflammation

Language: Английский

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Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression

Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: 30(9), P. 2092 - 2103

Published: Aug. 4, 2023

Abstract Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by central nervous (CNS) demyelination resulting in axonal injury and neurological deficits. Essentially, MS driven an auto-amplifying mechanism of inflammation cell death. Current therapies mainly focus on disease modification immunosuppression, while no treatment specifically focuses controlling death injury. Here, we report that ferroptosis, iron-catalyzed mode regulated (RCD), contributes to progression. Active lesions cerebrospinal fluid (CSF) patients revealed several signs reflected the presence elevated levels (labile) iron, peroxidized phospholipids lipid degradation products. Treatment with our candidate lead ferroptosis inhibitor, UAMC-3203, strongly delays relapse ameliorates progression preclinical model relapsing-remitting MS. In conclusion, results identify as detrimental targetable factor These findings create novel options for patients, along current immunosuppressive strategies.

Language: Английский

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Kaempferol as a therapeutic agent in Alzheimer’s disease: Evidence from preclinical studies

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 87, P. 101910 - 101910

Published: March 15, 2023

Language: Английский

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The beneficial role of autophagy in multiple sclerosis: Yes or No?

Autophagy, Journal Year: 2023, Volume and Issue: 20(2), P. 259 - 274

Published: Sept. 15, 2023

Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system (CNS) due to an increase abnormal peripherally auto-reactive T lymphocytes which elicit autoimmunity. The main pathophysiology MS myelin sheath damage by immune cells and defect in generation oligodendrocytes. Macroautophagy/autophagy critical degradation process that eliminates dysfunctional or superfluous cellular components. Autophagy has property double-edged sword it may have both beneficial detrimental effects on neuropathology. Therefore, this review illustrates protective harmful autophagy with regard disease. prevents progression reducing oxidative stress inflammatory disorders. In contrast, over-activated associated neuropathology case use inhibitors alleviate pathogenesis MS. Furthermore, provokes activation different supporting play intricate role functions modulation regulating cell proliferation related demyelination remyelination. enhances remyelination increasing activity oligodendrocytes, astrocytes. However, induces activating microglia cells. conclusion, specific autophagic activators astrocytes, dendritic (DCs), induce against

Language: Английский

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The potential therapeutic effect of statins in multiple sclerosis: beneficial or detrimental effects

Inflammopharmacology, Journal Year: 2023, Volume and Issue: 31(4), P. 1671 - 1682

Published: May 9, 2023

Language: Английский

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Therapeutic Potential of Natural Compounds in Neurodegenerative Diseases: Insights from Clinical Trials

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(1), P. 212 - 212

Published: Jan. 7, 2023

Neurodegenerative diseases are caused by the gradual loss of neurons’ function. These neurological illnesses remain incurable, and current medicines only alleviate symptoms. Given social economic burden rising frequency neurodegenerative diseases, there is an urgent need for development appropriate therapeutics. Natural compounds gaining popularity as alternatives to synthetic drugs due their neuroprotective properties higher biocompatibility. While natural compounds’ therapeutic effects disease treatment have been investigated in numerous vitro vivo studies, few moved clinical trials. This article provides first systematic review trials evaluating safety efficacy five most prevalent disorders: Alzheimer’s disease, Parkinson’s multiple sclerosis, amyotrophic lateral Huntington’s disease.

Language: Английский

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Significance of Programmed Cell Death Pathways in Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9947 - 9947

Published: Sept. 15, 2024

Programmed cell death (PCD) is a form of distinct from accidental (ACD) and also referred to as regulated (RCD). Typically, PCD signaling events are precisely by various biomolecules in both spatial temporal contexts promote neuronal development, establish neural architecture, shape the central nervous system (CNS), although role extends beyond CNS. Abnormalities cascades contribute irreversible loss cells function, leading onset progression neurodegenerative diseases. In this review, we summarize molecular processes features different modalities PCD, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, other novel forms their effects on pathogenesis diseases, such Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), multiple (MS), traumatic brain injury (TBI), stroke. Additionally, examine key factors involved these pathways discuss potential for development therapeutic targets strategies. Therefore, strategies targeting inhibition or facilitation offer promising approach clinical applications treating

Language: Английский

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Oxidative stress involvement in the molecular pathogenesis and progression of multiple sclerosis: a literature review

Reviews in the Neurosciences, Journal Year: 2024, Volume and Issue: 35(3), P. 355 - 371

Published: Jan. 1, 2024

Abstract Multiple sclerosis (MS) is an autoimmune debilitating disease of the central nervous system caused by a mosaic interactions between genetic predisposition and environmental factors. The pathological hallmarks MS are chronic inflammation, demyelination, neurodegeneration. Oxidative stress, state imbalance production reactive species antioxidant defense mechanisms, considered one key contributors in pathophysiology MS. This review comprehensive overview cellular molecular mechanisms which oxidant contribute to initiation progression including mitochondrial dysfunction, disruption various signaling pathways, response activation. detrimental effects oxidative stress on neurons, oligodendrocytes, astrocytes, as well role oxidants promoting perpetuating axonal damage, discussed. Finally, this also points out therapeutic potential synthetic antioxidants that must be evaluated clinical trials patients with

Language: Английский

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Multiple sclerosis plasma IgG aggregates induce complement-dependent neuronal apoptosis

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(4)

Published: April 8, 2023

Abstract Grey matter pathology is central to the progression of multiple sclerosis (MS). We discovered that MS plasma immunoglobulin G (IgG) antibodies, mainly IgG1, form large aggregates (>100 nm) which are retained in flow-through after binding Protein A. Utilizing an annexin V live-cell apoptosis detection assay, we demonstrated six times higher levels neuronal induced by IgG ( n = 190, from two cohorts) compared other neurological disorders 116) and healthy donors 44). aggregate-mediated, complement-dependent was evaluated model systems including primary human neurons, astrocytes, neuroblastoma SH-SY5Y cells, newborn mouse brain slices. Immunocytochemistry revealed co-deposition IgG, early late complement activation products (C1q, C3b, membrane attack complex C5b9), as well active caspase 3 treated cells. Furthermore, found cytotoxic antibodies not present flow-through, nor paired plasma. The can be inhibited depletion, disruption aggregates, pan-caspase inhibitor, completely abolished digestion with IgG-cleaving enzyme IdeS. Transmission electron microscopy nanoparticle tracking analysis sizes greater than 100 nm. Our data support pathological role corroborate their connection axonal damage, suggesting may a mechanism neurodegeneration MS.

Language: Английский

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Matrine mediated neuroprotective potential in experimental multiple sclerosis: Evidence from CSF, blood markers, brain samples and in-silico investigations

Journal of Neuroimmunology, Journal Year: 2023, Volume and Issue: 384, P. 578200 - 578200

Published: Sept. 16, 2023

Language: Английский

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