Alzheimers mast cell

The purpose of this focused review is to develop a consolidated hypothesis as to the causes and mechanisms of central sensitization and a related model for a treatment approach using Systemic Manual Therapy (SMT). The key to understanding central sensitization is a firm grasp on structure and function of the Locus-coeruleus noradrenaline system (LC-NA). This system uses an elaborate switching mechanism to control the level and rate of activation of multiple systems. This review evaluates the mechanisms and temporal relationships behind four components: salient stimuli, threat coding, aberrant afferent input, and oxidative stress...

Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by extracellular senile plaques and the formation of intracellular neurofibrillary tangles. The accumulation of toxic beta-amyloid (Aβ) induces the overproduction of reactive oxygen species (ROS), nitric oxide (NO) and pro-inflammatory cytokines. Accumulating studies suggest that neuroinflammatory mechanism plays an important role in the occurrence and development of AD. Microglia, astrocytes, macrophages, mast cells and T cells are involved in the pathogenesis of AD through neuroimmune mechanisms and inflammatory reactions...

Cognitive decline is believed to be associated with neurodegenerative processes involving excitotoxicity, oxidative damage, inflammation, and microvascular and blood-brain barrier dysfunction. Interestingly, research evidence suggests upregulated synthesis of lipid signaling molecules as an endogenous attempt to contrast such neurodegeneration-related pathophysiological mechanisms, restore homeostatic balance, and prevent further damage. Among these naturally occurring molecules, palmitoylethanolamide (PEA) has been independently associated with neuroprotective and anti-inflammatory properties, raising interest into the possibility that its supplementation might represent a novel therapeutic approach in supporting the body-own regulation of many pathophysiological processes potentially contributing to neurocognitive disorders...

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and manifests as progressive memory loss and cognitive dysfunction. Neuroinflammation plays an important role in the development of Alzheimer's disease and anti-inflammatory drugs reduce the risk of the disease. However, the immune microenvironment in the brains of patients with Alzheimer's disease remains unclear, and the mechanisms by which anti-inflammatory drugs improve Alzheimer's disease have not been clearly elucidated. This study aimed to provide an overview of the immune cell composition in the entorhinal cortex of patients with Alzheimer's disease based on the transcriptomes and signature genes of different immune cells and to explore potential therapeutic targets based on the relevance of drug targets...

Alzheimer's disease (AD) is an intractable and progressive neurodegenerative disorder that can lead to severe cognitive decline, impaired speech, short-term memory loss, and finally an inability to function in daily life. For patients, their families, and even all of society, AD can impart great emotional pressure and economic costs. Therefore, this study aimed to investigate potential diagnostic biomarkers of AD. Using the Gene Expression Omnibus (GEO) database, the expression profiles of genes were extracted from the GSE5281, GSE28146, and GSE48350 microarray datasets...

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease that leads to cognitive impairment and memory loss. Currently, the pathogenesis and underlying causative genes of AD remain unclear, and there exists no effective treatment for this disease. This study explored AD-related diagnostic and therapeutic biomarkers from the perspective of immune infiltration by analyzing public data from the NCBI Gene Expression Omnibus database. Method: In this study, weighted gene co-expression network analysis (WGCNA) was conducted to identify modules and hub genes contributing to AD development...

Objective: As a chronic neurodegenerative disorder, Alzheimer's disease (AD) is the most common form of progressive dementia. The purpose of this study was to identify diagnostic signatures of AD and the effect of immune cell infiltration in this pathology. Methods: The expression profiles of GSE109887, GSE122063, GSE28146, and GSE1297 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between AD and control brain samples...

BACKGROUND: Tau neurofibrillary tangles and senile plaques comprised of insoluble amyloid beta are the major histopathological hallmarks of Alzheimer's disease (AD). More than 85% of autopsy-confirmed AD cases also exhibit some degree of cerebral amyloid angiopathy (CAA), which is characterized by amyloid beta peptide deposits predominantly in blood vessels in the meningeal and intracerebral blood vessels. Consequently, CAA predisposes individuals with AD to cerebral infarction and hemorrhages, accounting for ∼20% of cases in the elderly, which could lead to faster cognitive decline through neurovascular pathway dysfunction...

BACKGROUND: Alzheimer's disease is pathologically defined by the presence of extracellular amyloid beta plaques and intracellular tau tangles, resulting in neurodegeneration and reactive gliosis in affected brain regions such as temporal cortex (TCX). The degree and distribution of AD pathology can be defined by Braak stage (tau) and Thal phase (amyloid). Brain tissue is comprised of multiple cell types that have different molecular profiles, the proportions of which can vary between individuals and in response to disease; creating challenges for the interpretation of bulk tissue transcriptome profiling study...

BACKGROUND: The lncRNA BACE1-AS was identified as a plasma molecular marker in the early diagnosis of Alzheimer's disease, but its role in tumors remains poorly defined. METHODS: The expression patterns, genomic mutation, and prognostic significance of BACE1-AS in pan-cancers were compared by analyzing 32 types of tumors from The Cancer Genome Atlas and cBioPortal databases. The relationships between BACE1-AS expression levels and the degree of immune cell infiltration, immune components, and immune-related genes were explored...

Alzheimer's disease (AD), an extremely common neurodegenerative disorder of the older generation, is one of the leading causes of death globally. Besides the conventional hallmarks i.e. Amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), neuroinflammation also serves as a major contributing factor in the pathogenesis of AD. There are mounting evidences to support the fundamental role of cellular (microglia, astrocytes, mast cells, and T-cells) and molecular (cytokines, chemokines, caspases, and complement proteins) influencers of neuroinflammation in producing/promoting neurodegeneration and dementia in AD...

Canine and feline cognitive dysfunction syndrome is a common neurodegenerative disorder of old age and a natural model of human Alzheimer's disease. With the unavoidable expanding life expectancy, an increasing number of small animals will be affected. Although there is no cure, early detection and intervention are vitally important to delay cognitive decline. Knowledge of cellular and molecular mechanisms underlying disease onset and progression is an equally decisive factor for developing effective approaches...

The actual standard treatment for mild-to-moderately severe Alzheimer's disease only attacks its symptoms. Masitinib is a potent and selective phenylaminothiazole-type tyrosine kinase inhibitor which is currently in Phase III studies for the treatment of Alzheimer's disease (AD) with the aim of modifying its evolution and with multiple pharmacological targets such as inhibition of mast cells activity, inhibition of microglia activation, modulation of Aβ and Tau protein signaling pathway and prevention of synaptic damage...

Cholesterol and 24-hydroxycholesterol are the most abundant brain sterols and represent the substrate and product, respectively, of cytochrome P450 46A1 (CYP46A1), a CNS-specific enzyme. CYP46A1 controls cholesterol elimination and turnover in the brain, the two processes that determine the rate of brain sterol flux through the plasma membranes and thereby the properties of these membranes. Brain sterol flux is decreased in Cyp46a1-/- mice compared to wild-type mice and increased in 5XFAD mice (a model of Alzheimer's disease) when they are treated with a small dose of efavirenz, a CYP46A1 activator...

Soybeans are rich in proteins and lipids and have become a staple part of the human diet. Besides their nutritional excellence, they have also been shown to contain various functional components, including isoflavones, and have consequently received increasing attention as a functional food item. Isoflavones are structurally similar to 17-β-estradiol and bind to estrogen receptors (ERα and ERβ). The estrogenic activity of isoflavones ranges from a hundredth to a thousandth of that of estrogen itself. Isoflavones play a role in regulating the effects of estrogen in the human body, depending on the situation...

Citrullination is an important post-translational modification implicated in many diseases including rheumatoid arthritis (RA), Alzheimer's disease, and cancer. Neutrophil and mast cells have different expression profiles for protein-arginine deiminases (PADs), and ionomycin-induced activation makes them an ideal cellular model to study proteins susceptible to citrullination. We performed high-resolution mass spectrometry and stringent data filtration to identify citrullination sites in neutrophil and mast cells treated with and without ionomycin...

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Cromolyn is a known mast cell stabilizer and is approved for treatment of asthma and for other allergic indications. Cromolyn, in a new redesigned dry powder formulation, is being tested in a pivotal clinical trial in combination with low dose ibuprofen to treat early Alzheimer's Disease (AD) subjects. To better understand the mechanistic effect cromolyn has in slowing down or halting the neuroinflammatory response associated with AD progression, we tested the effect of cromolyn to dampen the inflammatory response in the human HMC3 microglia cell line...

Corticotropin-releasing hormone is a critical component of the hypothalamic-pituitary-adrenal axis, which plays a major role in the body's immune response to stress. Mast cells are both sensors and effectors in the interaction between the nervous and immune systems. As first responders to stress, mast cells can initiate, amplify and prolong neuroimmune responses upon activation. Corticotropin-releasing hormone plays a pivotal role in triggering stress responses and related diseases by acting on its receptors in mast cells...

Considered relevant during allergy responses, numerous observations have also identified mast cells (MCs) as critical effectors during the progression and modulation of several neuroinflammatory conditions, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). MC granules contain a plethora of constituents, including growth factors, cytokines, chemokines, and mitogen factors. The release of these bioactive substances from MCs occurs through distinct pathways that are initiated by the activation of specific plasma membrane receptors/channels...