Mast cell and astrocyte hemichannels and their role in alzheimer’s disease, als, and harmful stress conditions

Paloma Andrea Harcha, Polett Garcés, Cristian Arredondo, Germán Fernández, Juan Carlos Sáez, Brigitte van Zundert

Research output: Contribution to journalReview articlepeer-review

21 Citations (Scopus)


Considered relevant during allergy responses, numerous observations have also identified mast cells (MCs) as critical effectors during the progression and modulation of several neuroin-flammatory conditions, including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). MC granules contain a plethora of constituents, including growth factors, cytokines, chemo-kines, 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 condi-tions. 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 (TNFα), apoliprotein E (ApoE), and certain miR-NAs—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.

Original languageEnglish
Article number1924
Pages (from-to)1-19
Number of pages19
JournalInternational Journal of Molecular Sciences
Issue number4
Publication statusPublished - 2 Feb 2021


  • Connexin
  • Degranulation
  • Gap junction channels
  • Glial cells
  • Hemichannels
  • Inflammation
  • Mast cells
  • Neurodegeneration
  • Pannexin
  • Pro-inflammatory compounds

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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