Impact of Mast Cell Activation on Neurodegeneration: A Potential Role for Gut–Brain Axis and Helicobacter pylori Infection
Abstract
:1. Introduction
2. Methodology
3. Neuroinflammation and Neurodegenerative Diseases
4. Mast Cells (MCs)
5. Mast Cells (MCs) and the Gut–Brain Axis (GBA)
6. Helicobacter pylori and Neurodegenerative Diseases
6.1. Alzheimer’s Disease (AD)
6.2. Parkinson’s Disease (PD)
6.3. Amyotrophic Lateral Sclerosis (ALS)
6.4. Huntington’s Disease (HD)
6.5. Multiple Sclerosis (MS)
7. Mast Cells (MCs) and Mechanisms of Neuroinflammation in Neurodegenerative Diseases
7.1. Mast Cells (MCs) in Alzheimer’s Disease (AD)
7.2. Mast Cells (MCs) in Parkinson’s Disease (PD)
7.3. Mast Cells (MCs) in Amyotrophic Lateral Sclerosis (ALS)
7.4. Mast Cells (MCs) in Huntington’s Disease (HD)
7.5. Mast Cells (MCs) in Multiple Sclerosis (MS)
8. Impact of Gut–Brain Axis (GBA) and the Activation of Mast Cells (MCs) on Neurodegeneration: A Potential Role for Hp Infection
9. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Disease | Major Disease Mechanisms | Evidence of Neuroinflammation /Key Players | Evidence of MC Involvement |
---|---|---|---|
AD | oxidative stress [132] | IL-1, IL-6, IFNγ [133,134,135] | MCs recruited into amyloid plaques [133,134,135] |
hyperphosphorylation of tau protein [136] | phagocyted amyloid particles in MCs in skin and gastric samples—histamine release [137] | ||
Aβ accumulation [138] | SAA causes MCs degranulation, cytokine release (TNF-α and IL-1) and chemotaxis [137] | ||
impairment of cholinergic transmission [139] | MC granule material causes SAA degradation into proto-fibrillar intermediates [140]. | ||
Aβ contributes to the degranulation of prefrontal cortical MCs, via the enhancement of Cx43 and Panx1 HC flux [137]. | |||
MCs detect low-solubility amyloid particles and to migrate to plaque sites, where they trigger the release of inflammatory mediators and disrupt the BBB [137]. | |||
MCs release MMP 2 and 9 and VEGF, leading to vascular leakage, CNS leukocyte infiltration, and edema [141]. | |||
MCs detect IL-33 and act as early responders to brain injury via the release of pre-stored TNF [142] and VEGFs thus further recruiting leukocytes and MCs [143,144,145]. | |||
MCs in stress-induced inflammation: release of CRH and further activation of MCs and microglia. Chronic stress triggers MC degranulation causing pro- inflammatory mediator release, synaptic loss, BBB disruption and neuroinflammation [146,147]. | |||
PD | loss of DA neurons in the SN and VTA [148] | Activated microglia and astrocytes present in areas with midbrain DA neuron loss [149] | Brain MCs neurotoxicity in the SN [150]. |
reduced DA transmission to STR [148] | Accumulation of misfolded α-synuclein linked to dysregulated immune responses in the CNS [151]. | Administration of MPTP after MC reconstitution in rats shown to increase oxidative stress and to alter levels of MDA, GSH, SOD and GPx [152]. | |
accumulation of α-synuclein [152] | PD-associated polymorphisms in the HLA-DR gene [151]. | MCs are attracted and activated in the SN region of MPTP-induced mice: releasing inflammatory mediators (histamine, LTs, TNF-α, and IL-1, thus contributing to TH+ DA neuron loss in the SN [153] | |
intracellular mitochondrial dysfunction-induced ROS generation [152] | Increased activated MCs in PD brains, particularly in the midbrain and the striatum and increased IL-33 expression linked to cell injury [146]. | ||
dysfunction in the ubiquitin-proteasomal and autophagy- lysosomal system [152] | NLRP3 inflammasome’s involvement in Parkinson’s disease [132,154,155]. peripheral tissue MCs in CAPS patients express inflammasomes and produce IL-1 [156]—potential role for CNS MCs Limitation: CNS MC expression of the NLRP3 inflammasome has not been directly studied | ||
ALS | degeneration of motor neurons [157] | Reactive immune cells in postmortem tissue of patients with familial and sporadic ALS [158,159]. | Degranulating MCs present in the quadriceps muscle of patients with ALS [158,159] |
distal motor axonopathy [157] | MCs and neutrophils surrounding motor axons in SOD1G93A rats with ALS [158,159] | ||
impaired axonal transport [157] | Masitinib results in reduced infiltration by MCs and neutrophils, ameliorates axonal pathology and secondary demyelination, and hinders the loss of type 2B myofibers in SOD1G93A rats [158,159] | ||
mitochondrial function defect [157] | The degree of MC degranulation corresponds to clinical disease endpoints in SOD1G93A mice [160]. | ||
MCs are regarded to enhance vascular permeability in the context of neuroinflammation, thus triggering further neutrophil recruitment, clustering and activation [157,161,162,163]. | |||
Presence of MCs and many c-Kit+ progenitors in the motor neuron-vascular niche [164] | |||
HD | production of a mHTT | Reactive astrocytes have been reported in pre-clinical stages of HD. Their presence correlates with later disease severity [165]. | mHTT promotes TLR-4 receptor internalization, thus affecting MC activation [166] |
Excitatory neurotoxicity caused by mHTT in the striatum and cortex | Reactive microglia have been reported in the striatum and cortex of HD, accompanying neuron loss, in postmortem brains [167]. | ||
MS | auto-reactive T cells recognizing CNS myelin antigens | Activation of the adaptive immune system [168] | MCs may act as antigen-presenting cells towards T cells [147,169] |
multi-focal demyelination | Microglia activation [168] | MCs disrupt the blood–brain barrier [170] | |
neurodegeneration | MC inflammasome plays pivotal role in the meningeal inflammation in EAE [171]. | ||
EAE development involves MC accumulation in the CNS [172,173]. |
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Boziki, M.; Theotokis, P.; Kesidou, E.; Nella, M.; Bakirtzis, C.; Karafoulidou, E.; Tzitiridou-Chatzopoulou, M.; Doulberis, M.; Kazakos, E.; Deretzi, G.; et al. Impact of Mast Cell Activation on Neurodegeneration: A Potential Role for Gut–Brain Axis and Helicobacter pylori Infection. Neurol. Int. 2024, 16, 1750-1778. https://doi.org/10.3390/neurolint16060127
Boziki M, Theotokis P, Kesidou E, Nella M, Bakirtzis C, Karafoulidou E, Tzitiridou-Chatzopoulou M, Doulberis M, Kazakos E, Deretzi G, et al. Impact of Mast Cell Activation on Neurodegeneration: A Potential Role for Gut–Brain Axis and Helicobacter pylori Infection. Neurology International. 2024; 16(6):1750-1778. https://doi.org/10.3390/neurolint16060127
Chicago/Turabian StyleBoziki, Marina, Paschalis Theotokis, Evangelia Kesidou, Maria Nella, Christos Bakirtzis, Eleni Karafoulidou, Maria Tzitiridou-Chatzopoulou, Michael Doulberis, Evangelos Kazakos, Georgia Deretzi, and et al. 2024. "Impact of Mast Cell Activation on Neurodegeneration: A Potential Role for Gut–Brain Axis and Helicobacter pylori Infection" Neurology International 16, no. 6: 1750-1778. https://doi.org/10.3390/neurolint16060127
APA StyleBoziki, M., Theotokis, P., Kesidou, E., Nella, M., Bakirtzis, C., Karafoulidou, E., Tzitiridou-Chatzopoulou, M., Doulberis, M., Kazakos, E., Deretzi, G., Grigoriadis, N., & Kountouras, J. (2024). Impact of Mast Cell Activation on Neurodegeneration: A Potential Role for Gut–Brain Axis and Helicobacter pylori Infection. Neurology International, 16(6), 1750-1778. https://doi.org/10.3390/neurolint16060127