The Role of Mast Cells in Alzheimer’s Disease

Shaik-Dasthagirisaheb, Yasdani B.; Conti, Pio

doi:10.17219/acem/61914

Cited by 49 publications

(42 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We speculate that this release may involve PAR-2, mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) pathways as reported previously for microglial activation by proteases (Zhang et al, 2012). Our current results and previous other reports have shown that mast cell proteases act as neuroinflammatory mediators in the neuroinflammatory disorders including PD (Zhang et al, 2012; Shaik-Dasthagirisaheb and Conti, 2016). We did not measure MMCP-6 and MMCP-7 in this study, as the exact ELISA kits for their measurements are not available.…”

Section: Discussionsupporting

confidence: 86%

Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

Kempuraj

Selvakumar

Zaheer

et al. 2017

J Neuroimmune Pharmacol

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a progressive movement disorder characterized by neuroinflammation and dopaminergic neurodegeneration in the brain. 1-methyl-4-phenylpyridinium (MPP+), a metabolite of the parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces the release of inflammatory mediators from glial cells and neurons. Glia maturation factor (GMF), a brain proinflammatory protein, MPP+, and mast cell-derived inflammatory mediators induce neurodegeneration which eventually leads to PD. However, the precise mechanisms underlying interaction between glial cells, neurons and mast cells in PD still remain elusive. In the present study, mouse bone marrow-derived mast cells (BMMCs) and mouse fetal brain-derived mixed glia/neurons, astrocytes and neurons were incubated with MPP+, GMF and mast cell-derived inflammatory mediators mouse mast cell protease-6 (MMCP-6), MMCP-7 or tryptase/brain-specific serine protease-4 (tryptase/BSSP-4). Inflammatory mediators released from these cells in the culture medium were quantitated by enzyme-linked immunosorbent assay. Neurodegeneration was quantified by measuring total neurite outgrowth following microtubule-associated protein-2 immunocytochemistry. MPP+− induced significant neurodegeneration with reduced total neurite outgrowth. MPP+− induced the release of tryptase/BSSP-4 from the mouse mast cells, and tryptase/BSSP-4 induced chemokine (C-C motif) ligand 2 (CCL2) release from astrocytes and glia/neurons. Overall our results suggest that MPP+, GMF, MMCP-6 or MMCP-7 stimulate glia/neurons, astrocytes or neurons to release CCL2 and matrix metalloproteinase-3. Additionally, CD40L expression is increased in BMMCs after incubation with MPP+ in a co-culture system consisting of BMMCs and glia/neurons. We propose that mast cell interaction with glial cells and neurons during neuroinflammation can be explored as a new therapeutic target for PD.

show abstract

Section: Discussionsupporting

confidence: 86%

Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

Kempuraj

Selvakumar

Zaheer

et al. 2017

J Neuroimmune Pharmacol

View full text Add to dashboard Cite

show abstract

“…Mast cells are the important source of inflammatory mediators in the brain and their interactions with glial cells and neurons release the mediators including cytokines, proteases and reactive oxygen species [56]. Since there is an important role of neuroinflammation in the pathogenesis of Alzheimer's disease, therefore, the role of mast cells in initiating neuroinflammation and inducing a cognitive decline in Alzheimer's disease has been described [57]. Indeed, the distribution of mast cells near to the amyloid plaques has been described.…”

Section: Mast Cellsmentioning

confidence: 99%

Astroglial connexins and cognition: memory formation or deterioration?

Yang

et al. 2020

Bioscience Reports

View full text Add to dashboard Cite

Connexins are the membrane proteins that form high-conductance plasma membrane channels and are the important constituents of gap junctions and hemichannels. Among different types of connexins, connexin 43 is the most widely expressed and studied gap junction proteins in astrocytes. Due to the key involvement of astrocytes in memory impairment and abundant expression of connexins in astrocytes, astroglial connexins have been projected as key therapeutic targets for Alzheimer’s disease. On the other hand, the role of connexin gap junctions and hemichannels in memory formation and consolidation has also been reported. Moreover, deletion of these proteins and loss of gap junction communication result in loss of short-term spatial memory. Accordingly, both memory formation and memory deteriorating functions of astrocytes-located connexins have been documented. Physiologically expressed connexins may be involved in the memory formation, while pathologically increased expression of connexins with consequent excessive activation of astrocytes may induce neuronal injury and cognitive decline. The present review describes the memory formation as well as memory deteriorating functions of astroglial connexins in memory disorders of different etiology with possible mechanisms.

show abstract

“…Increased levels of ROS in AD could activate mast cells to release inflammatory mediators (Chelombitko et al, 2016 ). Several mast cell-derived inflammatory mediators are reported to be involved in the AD pathogenesis and its level of severity (Shaik-Dasthagirisaheb and Conti, 2016 ). Mast cells, in fact are similar to neurons with regard to synthesis and secretion of neurotrophic factors, responsiveness to neuropeptides and monoaminergic content such as dopamine (Purcell and Atterwill, 1995 ).…”

Section: Mast Cells Neuroinflammation and Admentioning

confidence: 99%

“…Mast cells play an important role in inflammatory pathogenesis such as anaphylactic reactions, asthma, allergy, arthritis, cardiovascular diseases, systemic mastocytosis, interstitial cystitis, psoriasis, atopic dermatitis, cancer and metastasis, endometriosis, obesity, ulcers, prostatitis, periodontitis, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) (Sant et al, 2007 ; Theoharides et al, 2008 , 2010 , 2012a ; Galli and Tsai, 2012 ; Kritikou et al, 2016 ; Suurmond et al, 2016 ). Additionally, we and others have shown that mast cells are also implicated in many neurological and neuroinflammatory conditions including brain injury, traumatic brain injury (TBI), stroke, Multiple sclerosis (MS), Experimental Autoimmune Encephalomyelitis (EAE), Parkinson's disease (PD), dementia, Alzheimer's disease (AD), intracerebral hemorrhage (ICH), neuropsychiatric disorders, stress conditions, sleep disorders, migraine, pain, headache, attention deficit disorder, autism, joint and muscle pain, and itching (Theoharides et al, 1995 , 2005 , 2016 ; Sayed et al, 2011 ; Karagkouni et al, 2013 ; Graziottin et al, 2014 ; Kempuraj et al, 2016a , b ; Moretti et al, 2016 ; Shaik-Dasthagirisaheb and Conti, 2016 ). Mast cell-derived inflammatory mediators increase blood brain barrier (BBB) permeability and activate brain resident immune cells such as microglia (Ribatti, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis

et al. 2017

View full text Add to dashboard Cite

Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD) pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH) from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD) is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases including AD. This review focusses on how mast cells in brain injuries, stress, and PTSD may promote the pathogenesis of AD. We suggest that inhibition of mast cells activation and brain cells associated inflammatory pathways in the brain injuries, stress, and PTSD can be explored as a new therapeutic target to delay or prevent the pathogenesis and severity of AD.

show abstract

The Role of Mast Cells in Alzheimer’s Disease

Cited by 49 publications

References 31 publications

Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

Cross-Talk between Glia, Neurons and Mast Cells in Neuroinflammation Associated with Parkinson’s Disease

Astroglial connexins and cognition: memory formation or deterioration?

Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis

Contact Info

Product

Resources

About