Common cytokine receptor gamma chain family cytokines activate MAPK, PI3K, and JAK/STAT pathways in microglia to influence Alzheimer’s Disease

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

Published: Sept. 11, 2024

Dementia is an umbrella term used to describe deterioration of cognitive function. It the seventh leading cause death and one major causes dependence among older people globally. Alzheimer's Disease (AD) contributes approximately 60-70% dementia cases characterized by accumulation amyloid plaques tau tangles in brain. Neuroinflammation now widely accepted as another disease hallmark, playing a role both response perpetuation processes. Microglia are brain-resident immune cells that initially effective at clearing but contribute damaging inflammatory milieu brain progresses. Circulating peripheral this environment through cytokine secretion, creating positive feedback loop with microglia. One group these peripherally derived cytokines acting on microglia common receptor γ chain family. These bind heterodimer receptors activate three signaling pathways: MAPK, PI3K, JAK/STAT. This perspective will look mechanisms pathways highlight future directions research potential therapeutics.

Language: Английский

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The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 386 - 386

Published: Jan. 9, 2025

The blood-brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from bloodstream into central nervous system (CNS). Neurodegenerative diseases such as Alzheimer's Parkinson's disease, well ischemic stroke, compromise integrity BBB. This leads to increased permeability infiltration harmful substances, thereby accelerating neurodegeneration. In this review, we explore mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, loss tight junction integrity, in patients with neurodegenerative diseases. We discuss how breakdown contributes neurotoxicity, abnormal accumulation pathological proteins, all which exacerbate neuronal damage facilitate disease progression. Furthermore, potential therapeutic strategies aimed at preserving or restoring function, anti-inflammatory treatments, antioxidant therapies, approaches enhance integrity. Given role neurodegeneration, maintaining its represents promising approach slow prevent progression

Language: Английский

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Neurodegenerative diseases and neuroinflammation-induced apoptosis

Open Life Sciences, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 1, 2025

Abstract Neuroinflammation represents a critical pathway in the brain for clearance of foreign bodies and maintenance homeostasis. When neuroinflammatory process is dysregulate, such as over-activation microglia, which results excessive accumulation free oxygen inflammatory factors brain, among other factors, it can lead to an imbalance homeostasis development various diseases. Recent research has indicated that numerous neurodegenerative diseases closely associated with neuroinflammation. The pathogenesis neuroinflammation intricate, involving alterations genes proteins, well activation inhibition signaling pathways. Furthermore, inflammation result neuronal cell apoptosis, further exacerbate extent disease. This article presents summary recent studies on relationship between apoptosis caused by aim identify link two provide new ideas targets exploring pathogenesis, prevention treatment

Language: Английский

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Proteogenomic signature of risk of Alzheimer's disease and related dementia risk in individuals with a history of major depression disorder

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 12, 2024

The mechanisms linking a history of major depressive disorder (MDD) to an increased risk Alzheimer's disease and related dementia (ADRD) are not fully understood. Using the UK Biobank available proteomic genomic data, we evaluated biological both conditions. In participants with MDD at baseline (n=3,615), found that plasma levels NfL, GFAP, PSG1 were associated higher (HR=1.38; 1.37; 1.34, respectively; all adjusted p-values<0.05), while VGF, GET3, HPGDS lower incident ADRD (n=150) (HR=0.73; 0.71; 0.66, p-values<0.05) during mean follow-up 13.7 years (SD=2.2). Two-sample Mendelian randomization analysis using cis-pQTLs genetic instruments revealed protein expression apolipoprotein E IL-10 receptor subunit B causally linked ADRD. Finally, developed Proteomic Risk Score (PrRS

Language: Английский

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Microglia-mediated neuron death requires TNF and is exacerbated by mutant Huntingtin

Pharmacological Research, Journal Year: 2024, Volume and Issue: 209, P. 107443 - 107443

Published: Oct. 1, 2024

Language: Английский

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