Role of Connexin Hemichannels in Neurodegeneration

Orellana, Juan A.; Giaume, Christian; Sáez, Juan C.

doi:10.5772/28054

Cited by 1 publication

(1 citation statement)

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“…Connexins (Cx) and pannexins (Pn) are two membrane protein families forming hemichannels [259], creating connexons or gap junctions (GJs), allowing the exchange of molecules and ions as well as toxic substances, such as excitatory amino acids, with neighboring cells and promoting Ca 2+ overload [260,261]. In the CNS, GJs are widely expressed in astrocytes, where they couple these cells to create a functional syncytium [262], also allowing glutamate release [263] and favoring the inflammatory response [264].…”

Section: Hemichannelsmentioning

confidence: 99%

The Key Role of Astrocytes in Amyotrophic Lateral Sclerosis and Their Commitment to Glutamate Excitotoxicity

Provenzano,

Torazza,

Bonifacino

et al. 2023

IJMS

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In the last two decades, there has been increasing evidence supporting non-neuronal cells as active contributors to neurodegenerative disorders. Among glial cells, astrocytes play a pivotal role in driving amyotrophic lateral sclerosis (ALS) progression, leading the scientific community to focus on the “astrocytic signature” in ALS. Here, we summarized the main pathological mechanisms characterizing astrocyte contribution to MN damage and ALS progression, such as neuroinflammation, mitochondrial dysfunction, oxidative stress, energy metabolism impairment, miRNAs and extracellular vesicles contribution, autophagy dysfunction, protein misfolding, and altered neurotrophic factor release. Since glutamate excitotoxicity is one of the most relevant ALS features, we focused on the specific contribution of ALS astrocytes in this aspect, highlighting the known or potential molecular mechanisms by which astrocytes participate in increasing the extracellular glutamate level in ALS and, conversely, undergo the toxic effect of the excessive glutamate. In this scenario, astrocytes can behave as “producers” and “targets” of the high extracellular glutamate levels, going through changes that can affect themselves and, in turn, the neuronal and non-neuronal surrounding cells, thus actively impacting the ALS course. Moreover, this review aims to point out knowledge gaps that deserve further investigation.

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