The Role of IL-6 in Neurodegenerative Disorders

Shan, Chen; Zhang, Chao; Zhang, Chuanbao

doi:10.1007/s11064-023-04085-6

Cited by 8 publications

(3 citation statements)

References 152 publications

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“…It can contribute to neurodegeneration by promoting neuroinflammatory reactions, disrupting neuron homeostasis, and inducing neuronal damage. IL-6 can also affect protein kinase pathways and tau phosphorylation patterns [ 206 , 207 ].…”

Section: Inflammatory Biomarkersmentioning

confidence: 99%

From Gut to Brain: Uncovering Potential Serum Biomarkers Connecting Inflammatory Bowel Diseases to Neurodegenerative Diseases

Sarb,

Iacobescu

et al. 2024

IJMS

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Inflammatory bowel diseases (IBDs) are characterized by chronic gastrointestinal inflammation due to abnormal immune responses to gut microflora. The gut–brain axis is disrupted in IBDs, leading to neurobiological imbalances and affective symptoms. Systemic inflammation in IBDs affects the brain’s inflammatory response system, hormonal axis, and blood–brain barrier integrity, influencing the gut microbiota. This review aims to explore the association between dysregulations in the gut–brain axis, serum biomarkers, and the development of cognitive disorders. Studies suggest a potential association between IBDs and the development of neurodegeneration. The mechanisms include systemic inflammation, nutritional deficiency, GBA dysfunction, and the effect of genetics and comorbidities. The objective is to identify potential correlations and propose future research directions to understand the impact of altered microbiomes and intestinal barrier functions on neurodegeneration. Serum levels of vitamins, inflammatory and neuronal damage biomarkers, and neuronal growth factors have been investigated for their potential to predict the development of neurodegenerative diseases, but current results are inconclusive and require more studies.

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Section: Inflammatory Biomarkersmentioning

confidence: 99%

From Gut to Brain: Uncovering Potential Serum Biomarkers Connecting Inflammatory Bowel Diseases to Neurodegenerative Diseases

Sarb,

Iacobescu

et al. 2024

IJMS

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“…IL-6 exacerbates chronic neuroinflammation, affecting the blood-brain barrier (BBB) and influencing neuronal survival. Dysregulated IL-6 signaling contributes to neuroinflammation, releasing pro-inflammatory cytokines and reactive oxygen species, further damaging neurons, and impairing cognitive function in AD ( 83 ). Additionally, IL-6 can affect the integrity of the BBB, which regulates the passage of molecules and immune cells between the bloodstream and the brain.…”

Section: Il-6 In Neurological Disordersmentioning

confidence: 99%

The impact of interleukin-6 (IL-6) and mesenchymal stem cell-derived IL-6 on neurological conditions

Kerkis,

Silva,

Araldi

2024

Front. Immunol.

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Interleukin-6 (IL-6) is a versatile cytokine crucial for immune response modulation, inflammation regulation, and various physiological processes in the body. Its wide-ranging functions underscore its importance in maintaining health. Dysregulated IL-6 is closely associated with many diseases, making it a key research and therapeutic target. Elevated IL-6 levels in the central nervous system worsen neuroinflammation in neurodegenerative diseases by activating microglia and astrocytes and releasing pro-inflammatory cytokines and neurotoxic molecules. Moreover, dysregulated IL-6 weakens the blood-brain barrier, exacerbating neuroinflammation and neuronal damage by allowing peripheral immune cells and inflammatory mediators to enter the brain. Mesenchymal stem cells (MSCs) show promise in modulating neuroinflammation by regulating IL-6 levels. They effectively suppress pro-inflammatory cytokines, including IL-6, while promoting anti-inflammatory factors. This therapeutic approach highlights the importance of targeting IL-6 and other inflammatory mediators to alleviate neuroinflammation and its adverse effects on neurological disorders. This review provides a comprehensive overview of IL-6’s involvement in neurological disorders, examining endogenous IL-6 and IL-6 derived from MSCs. We explore IL-6’s mechanisms affecting neuronal function, survival, and immune modulation in the central nervous system. Additionally, we discuss the potential of MSC-derived IL-6 in neuroregeneration and neuroprotection. By elucidating IL-6’s interplay with neurological pathologies, this review offers insights into novel therapeutic strategies targeting IL-6 signaling pathways for neurological disorders.

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“…The cellular antioxidant system, composed of superoxide dismutase (SOD), catalase (CAT), peroxidase, and reduced glutathione (GSH), acts as a free radical scavenger, and neurodegeneration is promoted due to an imbalance in the defensive actions of antioxidants and overproduction of ROS. , Moreover, neuroinflammation, which is initially crucial for stimulating tissue repair and removing the brain’s cellular waste, could be a significant key factor in the pathogenesis and progression of various NDs in cases of persistence due to genetic mutations, trauma, and infection, which play their roles via proinflammatory agent release, including interleukin-6 (IL-6) and immune cell activation, leading to neuronal dysfunction and destruction. In fact, the engagement and overactivity of microglia and astrocytes in neuroinflammatory responses might be responsible for the pathogenesis of neurodegenerative diseases, especially Alzheimer’s disease, in which microglia play a vital role in responding to Aβ aggregation. − The major NDs include Alzheimer’s disease (AD), Parkinson’s disease (PD), ataxia, Huntington’s disease (HD), motor neuron disease, multiple system atrophy, and progressive supranuclear palsy, in which the main causes are reported to be the accumulation of amyloid β (Aβ), Tau, and α-synuclein in the form of insoluble fibrillary deposits with β-sheet structure in the brain of patients. , According to the Global Burden of Disease (GBD) study, a variety of conditions, including AD, PD, multiple sclerosis (MS), and epilepsy, as well as headache disorders such as migraine, tension-type headache, and medication-overuse headache, collectively contribute to 3% of the GBD. The top 50 causes of disability-adjusted life years (DALYs) include dementia, epilepsy, migraine, and stroke…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Activities and Molecular Mechanisms of Sinapic Acid in Neurological Disorders

Farzan,

Abedi,

Bhia

et al. 2024

ACS Chem. Neurosci.

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Sinapic acid (SA) is a phenylpropanoid derivative found in various natural sources that exhibits remarkable versatile properties, including antioxidant, anti-inflammatory, and metalchelating capabilities, establishing itself as a promising candidate for the prevention and treatment of conditions affecting the central nervous system, such as Alzheimer's disease (AD), Parkinson's disease (PD), ischemic stroke, and other neurological disorders. These effects also include neuroprotection in epilepsy models, as evidenced by a reduction in seizure-like behavior, cell death in specific hippocampal regions, and lowered neuroinflammatory markers. In AD, SA treatment enhances memory, reverses cognitive deficits, and attenuates astrocyte activation. SA also has positive effects on cognition by improving memory and lowering oxidative stress. This is shown by lower levels of oxidative stress markers, higher levels of antioxidant enzyme activity, and better memory retention. Additionally, in ischemic stroke and PD models, SA provides microglial protection and exerts anti-inflammatory effects. This review emphasizes SA's multifaceted neuroprotective properties and its potential role in the prevention and treatment of various brain disorders. Despite the need for further research to fully understand its mechanisms of action and clinical applicability, SA stands out as a valuable bioactive compound in the ongoing quest to combat neurodegenerative diseases and enhance the quality of life for affected individuals.

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The Role of IL-6 in Neurodegenerative Disorders

Cited by 8 publications

References 152 publications

From Gut to Brain: Uncovering Potential Serum Biomarkers Connecting Inflammatory Bowel Diseases to Neurodegenerative Diseases

From Gut to Brain: Uncovering Potential Serum Biomarkers Connecting Inflammatory Bowel Diseases to Neurodegenerative Diseases

The impact of interleukin-6 (IL-6) and mesenchymal stem cell-derived IL-6 on neurological conditions

Pharmacological Activities and Molecular Mechanisms of Sinapic Acid in Neurological Disorders

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