Mast Cells in Age-Related Neurodegeneration and Neuroinflammation

Of late, it is becoming clear that the dysfunction of immune cells of the central nervous system, such as microglia, is an important part of neurodegeneration. Growing degrees of cellular senescence in these cell populations, leading to inflammatory signaling, appears to be significant in the progression of Alzheimer's disease, for example. There are many distinct types of supporting cell in the brain, however. This short open access review paper discusses the evidence for dysfunction of the immune cells known as mast cells to be relevant to the progression of chronic inflammation and neurodegeneration in the aging brain.

Mast cells are "first responders" that become activated with exposure to a diverse array of stimuli, from allergens and antigens to neuropeptides, trauma, and drugs. Activated mast cells are multifunctional effector cells that exert a variety of both immediate and delayed actions.

Neuroinflammation, which is now recognized as a primary pathological component of diseases such as multiple sclerosis, is gaining acceptance as an underlying component of most, if not all, neurodegenerative diseases. Whereas past focus has predominantly centered on glial cells of the central nervous system, recently mast cells have emerged as potential key players in both neuroinflammation and neurodegenerative diseases. Mast cells are well positioned for such a role owing to their ability to affect both their microenvironment and neighboring cells including T cells, astrocytes, microglia, and neurons. The secretory granules of mast cells contain an arsenal of preformed/stored immunomodulators, neuromodulators, proteases, amines, and growth factors that enable complex cross-communication, which can be both unidirectional and bidirectional. Mast cells can also affect disruption/permeabilization of the blood-brain barrier and this has the potential for dramatically altering the neuroinflammatory state.

With respect to Alzheimer's disease (AD), Parkinson's disease (PD), ALS, and Huntington's disease (HD), mast cell perturbation of the blood-brain barrier appears to share a commonality. Moreover, mast cells have been found to home to sites of amyloid deposition in AD; and, an inhibitor of mast cell function was shown to reduce cognitive decline in AD patients. Mast cell interactions with neurons and glial cells have also been implicated in PD pathogenesis. Emerging evidence suggests that mast cell autocrine signaling may contribute to ALS: The mast cell chemoattractant, IL-15, is elevated in the serum and cerebrospinal fluid of ALS patients; and, mast cells expressing IL-17 have been found in the spinal cord of ALS patients. Plasma levels of cytokines (IL-6, IL-8), known to affect mast cell activation, have been correlated with functional scores in HD patients suggesting the possible involvement of mast cells in the pathogenesis of HD.



This was posted the day before my daughter's intractable (and life-threatening) vomiting started - most likely due to Mast Cell Activation Syndrome. A couple of weeks after tending to her in the hospital, I also started to have symptoms of MCAS; I believe the disease was, in our cases, initiated by a pathogen.

Previously, I had ignored mast cells - always focusing on macrophages and microglia - and realize now what a huge oversight that was. I suspect mast cells play a pivotal role in many diseases, including aging.

Quercetin and fisetin are both mast cell stabilizers.

Posted by: CD at September 5th, 2019 9:06 AM

It was just recently , i have found immune function of MC and their activation is much more complex than expected. I had an allergic reaction soon after birth, presenting as abdomen problem , IBS alternate D_C dominant. In my 18 and second year of university course , the dragon wok up again and again in second year of properly diagnosis made a big problem till i wrote its episodes as calmness and flare up in my life....i was on benzodiazepines for 2 control dizziness and brain fog , periodically headaches....i was beautiful girl but stress destroyed it focus on stress and prescribed anti anxiety....but it was only a short remedy based on simple idea .....the issue was indeed a less known syndrome called MCAS. it respond to MC Stablizer and H1 blockers particularly hydroxyzine and damaged tissue gradually was repaired, faster than imaginable.
I am PHD in medical sciences and as a scientist i am in believing much more efforts is necessary to recognize molecular signaling to find root of diseases as well as facilitating FDA approval to discovery of off_label use for at lease well known drug. i have found many till now, while many patients dye due to drug shortage and long time clinical trial....unfortunately many people are discover the result by personalised therapy before the clinical results revealed.these data with a rough approach resembling clinical trials. Some example are azithromycine and dapson anti inflammatory effect, valporate for migraine and so on.

Posted by: Anna at April 20th, 2020 11:15 AM

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