Neuroimmune regulation of microglial activity involved in neuroinflammation and neurodegenerative diseases

González, Hugo; Elgueta, Daniela; Montoya, Andro; Pacheco, Rodrigo

doi:10.1016/j.jneuroim.2014.07.012

Cited by 293 publications

(188 citation statements)

References 148 publications

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“…Given the central role of cytokines in the brain under normal or disease conditions, prolonged exposure to proinflammatory cytokines that promote neural injuries, e.g., tumor necrosis factor alpha (TNF-␣), IL-6, and IL-1␤, may aggravate neurodegenerative progression and compromise vulnerable neurons (201). Our knowledge of the systemic immune response to T. canis greatly exceeds that of the brain's immune response (202).…”

Section: Murine Models Of Neurological Inflammation Ubiquitin-proteamentioning

confidence: 99%

Cerebral Toxocariasis: Silent Progression to Neurodegenerative Disorders?

et al. 2015

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SUMMARY Toxocara canis and T. cati are highly prevalent nematode infections of the intestines of dogs and cats. In paratenic hosts, larvae do not mature in the intestine but instead migrate through the somatic tissues and organs of the body. The presence of these migrating larvae can contribute to pathology. Toxocara larvae can invade the brains of humans, and while case descriptions of cerebral toxocariasis are historically rare, improved diagnosis and greater awareness have contributed to increased detection. Despite this, cerebral or neurological toxocariasis (NT) remains a poorly understood phenomenon. Furthermore, our understanding of cognitive deficits due to toxocariasis in human populations remains particularly deficient. Recent data describe an enhanced expression of biomarkers associated with brain injury, such as GFAP, AβPP, transforming growth factor β1 (TGF-β1), NF-L, S100B, tTG, and p-tau, in mice receiving even low doses of Toxocara ova. Finally, this review outlines a hypothesis to explore the relationship between the presence of T. canis larvae in the brain and the progression of Alzheimer's disease (AD) due to enhanced AD-associated neurodegenerative biomarker expression.

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Section: Murine Models Of Neurological Inflammation Ubiquitin-proteamentioning

confidence: 99%

Cerebral Toxocariasis: Silent Progression to Neurodegenerative Disorders?

et al. 2015

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“…Once thought to be only a consequence of motor neuron death, neuroinflammation is now established as an important factor not only in the pathogenesis of ALS, but also in many other neurodegenerative diseases, including Parkinson's, Alzheimer's, multiple sclerosis, HIV-associated encephalopathy, and cerebrovascular disease [46][47][48][49][50][51]. Much of what has been learned in ALS regarding neuroinflammation has come through discoveries in these other neurodegenerative diseases.…”

mentioning

confidence: 99%

Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis

et al. 2015

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Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous disorder characterized by loss of motor neurons, resulting in paralysis and death. Multiple mechanisms of motor neuron injury have been implicated based upon the more than 20 different genetic causes of familial ALS. These inherited mutations compromise diverse motor neuron pathways leading to cell-autonomous injury. In the ALS transgenic mouse models, however, motor neurons do not die alone. Cell death is noncell-autonomous dependent upon a well orchestrated dialogue between motor neurons and surrounding glia and adaptive immune cells. The pathogenesis of ALS consists of 2 stages: an early neuroprotective stage and a later neurotoxic stage. During early phases of disease progression, the immune system is protective with glia and T cells, especially M2 macrophages/microglia, and T helper 2 cells and regulatory T cells, providing anti-inflammatory factors that sustain motor neuron viability. As the disease progresses and motor neuron injury accelerates, a second rapidly progressing phase develops, characterized by M1 macrophages/microglia, and proinflammatory T cells. In rapidly progressing ALS patients, as in transgenic mice, neuroprotective regulatory T cells are significantly decreased and neurotoxicity predominates. Our own therapeutic efforts are focused on modulating these neuroinflammatory pathways. This review will focus on the cellular players involved in neuroinflammation in ALS and current therapeutic strategies to enhance neuroprotection and suppress neurotoxicity with the goal of arresting the progressive and devastating nature of ALS.

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“…Translocation of NF-κB to the nucleus culminates in the secretion of proinflammatory molecules (IL-1β, IL-6, TNF-α, and IL-12). Activated astrocytes may also produce chemokines that recruit microglial cells, lymphocytes, and dendritic cells to the site of injury [57].…”

Section: Astrocytesmentioning

confidence: 99%

“…TNF-α, secreted both by microglia and astrocytes, can directly promote neuronal death by binding to its corresponding receptors (TNFRs). Evidence indicates that TNF-α induces apoptosis of mature oligodendrocytes in inflammatory demyelinating diseases such as multiple sclerosis [61,70] and plays a key role in neurodegeneration process observed in Parkinson's and Alzheimer's diseases [57].…”

Section: Microgliamentioning

confidence: 99%

The Role of NO/cGMP Signaling on Neuroinflammation: A New Therapeutic Opportunity

Peixoto¹,

Nunes²,

Rapôso³

2017

Mechanisms of Neuroinflammation

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The nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling appears to play a key role in inhibiting neuroinflammation and preventing the activation of a proapoptotic pathway, thereby promoting neural cell survival. In addition, evidence indicates that cGMP/protein kinase G (PKG) pathway is involved in the modulation of glial cell activity. Phosphodiesterase 5 (PDE5), which hydrolyzes cGMP in the inactive form, 5ʹGMP, is present throughout the body and brain and has emerged as a potential therapeutic target for diseases related to neuroinflammatory and neurodegenerative processes, since their inhibition leads to accumulation of cGMP. The objective of this chapter is to review current knowledge of NO/cGMP signaling pathways on neuroinflammation and the potential therapeutic use of PDE5 inhibitors (PDE5-Is) in neurological diseases. The extensive, while recent, literature on the effects of PDE-Is on Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD), Huntington's disease (HD), and stroke has been reviewed.

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Neuroimmune regulation of microglial activity involved in neuroinflammation and neurodegenerative diseases

Cited by 293 publications

References 148 publications

Cerebral Toxocariasis: Silent Progression to Neurodegenerative Disorders?

Cerebral Toxocariasis: Silent Progression to Neurodegenerative Disorders?

Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis

The Role of NO/cGMP Signaling on Neuroinflammation: A New Therapeutic Opportunity

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