UMMS Affiliation

Department of Neurology

Publication Date


Document Type



Amino Acids, Peptides, and Proteins | Biological Factors | Molecular Biology | Nervous System Diseases | Neuroscience and Neurobiology


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. Here, we focus on hemichannels (HCs) formed by connexins (Cxs) and pannexins (Panxs) proteins, and we described their contribution to MC degranulation in AD, ALS, and harmful stress conditions. Cx/Panx HCs are also expressed by astrocytes and are likely involved in the release of critical toxic amounts of soluble factors-such as glutamate, adenosine triphosphate (ATP), complement component 3 derivate C3a, tumor necrosis factor (TNFalpha), apoliprotein E (ApoE), and certain miRNAs-known to play a role in the pathogenesis of AD, ALS, and other neurodegenerative disorders. We propose that blocking HCs on MCs and glial cells offers a promising novel strategy for ameliorating the progression of neurodegenerative diseases by reducing the release of cytokines and other pro-inflammatory compounds.


connexin, degranulation, gap junction channels, glial cells, hemichannels, inflammation, mast cells, neurodegeneration, pannexin, pro-inflammatory compounds

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Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (

DOI of Published Version



Harcha PA, Garcés P, Arredondo C, Fernández G, Sáez JC, van Zundert B. Mast Cell and Astrocyte Hemichannels and Their Role in Alzheimer's Disease, ALS, and Harmful Stress Conditions. Int J Mol Sci. 2021 Feb 15;22(4):1924. doi: 10.3390/ijms22041924. PMID: 33672031; PMCID: PMC7919494. Link to article on publisher's site

Journal/Book/Conference Title

International journal of molecular sciences

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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.