Neuroinflammation in Neurodegenerative Disorders—a Review

Schain, Martin; Kreisl, William Charles

doi:10.1007/s11910-017-0733-2

Cited by 256 publications

(157 citation statements)

References 127 publications

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“…Neuroinflammation is known to directly and systemically contribute to the recruitment of peripheral inflammatory cells and increase BBB permeability in the neurodegenerative diseases (Hayley and Anisman, 2005; Ferrari and Tarelli, 2011; Espinosa-Oliva et al, 2014; Dendrou et al, 2016; McManus and Heneka, 2017; Schain and Kreisl, 2017). Peripheral infection and inflammation increases BBB permeability and neuroinflammation in the animal model of AD (Takeda et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration

Kempuraj

Thangavel

Selvakumar

et al. 2017

Front. Cell. Neurosci.

290

223

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Neuroinflammatory response is primarily a protective mechanism in the brain. However, excessive and chronic inflammatory responses can lead to deleterious effects involving immune cells, brain cells and signaling molecules. Neuroinflammation induces and accelerates pathogenesis of Parkinson’s disease (PD), Alzheimer’s disease (AD) and Multiple sclerosis (MS). Neuroinflammatory pathways are indicated as novel therapeutic targets for these diseases. Mast cells are immune cells of hematopoietic origin that regulate inflammation and upon activation release many proinflammatory mediators in systemic and central nervous system (CNS) inflammatory conditions. In addition, inflammatory mediators released from activated glial cells induce neurodegeneration in the brain. Systemic inflammation-derived proinflammatory cytokines/chemokines and other factors cause a breach in the blood brain-barrier (BBB) thereby allowing for the entry of immune/inflammatory cells including mast cell progenitors, mast cells and proinflammatory cytokines and chemokines into the brain. These peripheral-derived factors and intrinsically generated cytokines/chemokines, α-synuclein, corticotropin-releasing hormone (CRH), substance P (SP), beta amyloid 1–42 (Aβ1–42) peptide and amyloid precursor proteins can activate glial cells, T-cells and mast cells in the brain can induce additional release of inflammatory and neurotoxic molecules contributing to chronic neuroinflammation and neuronal death. The glia maturation factor (GMF), a proinflammatory protein discovered in our laboratory released from glia, activates mast cells to release inflammatory cytokines and chemokines. Chronic increase in the proinflammatory mediators induces neurotoxic Aβ and plaque formation in AD brains and neurodegeneration in PD brains. Glial cells, mast cells and T-cells can reactivate each other in neuroinflammatory conditions in the brain and augment neuroinflammation. Further, inflammatory mediators from the brain can also enter into the peripheral system through defective BBB, recruit immune cells into the brain, and exacerbate neuroinflammation. We suggest that mast cell-associated inflammatory mediators from systemic inflammation and brain could augment neuroinflammation and neurodegeneration in the brain. This review article addresses the role of some atypical inflammatory mediators that are associated with mast cell inflammation and their activation of glial cells to induce neurodegeneration.

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Section: Introductionmentioning

confidence: 99%

Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration

Kempuraj

Thangavel

Selvakumar

et al. 2017

Front. Cell. Neurosci.

290

223

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“…In addition to inhibiting proinflammatory cytokines, the upregulating the anti-inflammatory cytokines expression also plays an important role in anti-inflammatory effect of drugs (Schain andKreisl, 2017, Carlessi et al, 2019). In this study, we found that ASA Ⅵ could increase the expression and secretion of IL-10, a classic anti-inflammatory cytokine.…”

Section: Discussionmentioning

confidence: 99%

Asperosaponin VI inhibits LPS-induced inflammatory response by activating PPAR-γ pathway in primary microglia

Zhang

Xiao

et al. 2020

Preprint

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Microglia cells are the main mediators of neuroinflammation.Activation of microglia often aggravates the pathological process of various neurological diseases. Natural chemicals have unique advantages in inhibiting microglia-mediated neuroinflammation and improving neuronal function. Here, we examined the effects of asperosaponin Ⅵ (ASA Ⅵ) on LPS-activated primary microglia. Microglia were isolated from mice and pretreated with different doses of ASA Ⅵ, following lipopolysaccharide (LPS) administration. Activation and inflammatory response of microglia cells were evaluated by q-PCR, immunohistochemistry and ELISA. Signaling pathways were detected by western blotting. We found that the ASA Ⅵ inhibited the morphological expansion of microglia cells, decreased the expression and release of proinflammatory cytokines, and promoted the expression of antiinflammatory cytokines in a dose-dependent manner. ASA Ⅵ also activated PPAR-γ signaling pathway in LPS-treated microglia. The anti-inflammatory effects of ASA Ⅵ in microglia were blocked by treating PPAR-γ antagonist (GW9662). These results showed that ASA Ⅵ promote the transition of microglia cells from proinflammatory to anti-inflammatory by regulating PPAR-γ pathway.

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“…Most PET studies conducted to date in AD have shown positive results (Schain & Kreisl, 2017). For instance, studies found that 11 C-( R )-PK-11195 binding was increased in AD patients and correlated with clinical severity (Cagnin et al, 2001; Edison et al, 2008; Yokokura et al, 2011).…”

Section: Neuroinflammation In Alzheimer’s Diseasementioning

confidence: 99%

Imaging Translocator Protein as a Biomarker of Neuroinflammation in Dementia

Kreisl

Henter

Innis

2018

Advances in Pharmacology

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Neuroinflammation has long been considered a potential contributor to neurodegenerative disorders that result in dementia. Accumulation of abnormal protein aggregates in Alzheimer’s disease, frontotemporal dementia, and dementia with Lewy bodies is associated with the activation of microglia and astrocytes into proinflammatory states, and chronic low-level activation of glial cells likely contributes to the pathological changes observed in these and other neurodegenerative diseases. The 18 kDa translocator protein (TSPO) is a key biomarker for measuring inflammation in the brain via positron emission tomography (PET). Increased TSPO density has been observed in brain tissue from patients with neurodegenerative diseases and colocalizes to activated microglia and reactive astrocytes. Several radioligands have been developed to measure TSPO density in vivo with PET, and these have been used in clinical studies of different dementia syndromes. However, TSPO radioligands have limitations, including low specific-to-nonspecific signal and differential affinity to a polymorphism on the TSPO gene, which must be taken into consideration in designing and interpreting human PET studies. Nonetheless, most PET studies have shown that increased TSPO binding is associated with various dementias, suggesting that TSPO has potential as a biomarker to further explore the role of neuroinflammation in dementia pathogenesis and may prove useful in monitoring disease progression.

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Neuroinflammation in Neurodegenerative Disorders—a Review

Cited by 256 publications

References 127 publications

Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration

Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration

Asperosaponin VI inhibits LPS-induced inflammatory response by activating PPAR-γ pathway in primary microglia

Imaging Translocator Protein as a Biomarker of Neuroinflammation in Dementia

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