Impact of Mast Cell Activation on Neurodegeneration: A Potential Role for Gut-Brain Axis and Helicobacter pylori Infection

Abstract

Background: The innate immune response aims to prevent pathogens from entering the organism and/or to facilitate pathogen clearance. Innate immune cells, such as macrophages, mast cells (MCs), natural killer cells and neutrophils, bear pattern recognition receptors and are thus able to recognize common molecular patterns, such as pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs), the later occurring in the context of neuroinflammation. An inflammatory component in the pathology of otherwise "primary cerebrovascular and neurodegenerative" disease has recently been recognized and targeted as a means of therapeutic intervention. Activated MCs are multifunctional effector cells generated from hematopoietic stem cells that, together with dendritic cells, represent first-line immune defense mechanisms against pathogens and/or tissue destruction.

Methods: This review aims to summarize evidence of MC implication in the pathogenesis of neurodegenerative diseases, namely, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis.

Results: In view of recent evidence that the gut-brain axis may be implicated in the pathogenesis of neurodegenerative diseases and the characterization of the neuroinflammatory component in the pathology of these diseases, this review also focuses on MCs as potential mediators in the gut-brain axis bi-directional communication and the possible role of Helicobacter pylori, a gastric pathogen known to alter the gut-brain axis homeostasis towards local and systemic pro-inflammatory responses.

Conclusion: As MCs and Helicobacter pylori infection may offer targets of intervention with potential therapeutic implications for neurodegenerative disease, more clinical and translational evidence is needed to elucidate this field.

Keywords: Alzheimer’s disease; Helicobacter pylori; Parkinson’s disease; amyotrophic lateral sclerosis; gut–brain axis; mast cells; multiple sclerosis; neurodegeneration; neuroinflammation.

Figure 1

The gut–brain axis (GBA) as a bidirectional network. The figure illustrates the gut–brain axis as a bidirectional network controlled by hormonal, nervous, immunological, and metabolic signaling pathways. It shows how dysregulated mast cells disrupt the gut microbiome, leading to inflammation and gut barrier breakdown. The role of Helicobacter pylori is highlighted, showing its contribution to neurodegenerative diseases through immune mechanisms, including defective monocytes and molecular mimicry, which may lead to neuroinflammation and blood–brain barrier disruption. single-headed yellow arrows denote result; double-headed yellow arrows denote bi-directional interaction/communication; yellow lightning signs denote pathology.