Connexin and Pannexin Hemichannel Signaling in Neurodegeneration
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mechanism1107 wordssynced 2026-04-02
Connexin and Pannexin Hemichannel Signaling in Neurodegeneration
Overview
Connexins and pannexins are transmembrane channel proteins that form gap junctions and hemichannels, allowing direct communication between cells and between the intracellular and extracellular compartments. In the central nervous system, these channels play critical roles in neuronal function, glial signaling, and neuroimmune interactions. Dysregulation of connexin and pannexin signaling has been implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and stroke. This pathway page explores the molecular mechanisms by which these channels contribute to neurodegeneration and their potential as therapeutic targets.
Connexin and Pannexin Family
Connexins
Connexins are a family of 21 members in humans, named by their molecular weight (e.g., Cx26 = 26 kDa). Key connexins in the CNS include: [@orellana2020]
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Connexin and Pannexin Hemichannel Signaling in Neurodegeneration
Overview
Connexins and pannexins are transmembrane channel proteins that form gap junctions and hemichannels, allowing direct communication between cells and between the intracellular and extracellular compartments. In the central nervous system, these channels play critical roles in neuronal function, glial signaling, and neuroimmune interactions. Dysregulation of connexin and pannexin signaling has been implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and stroke. This pathway page explores the molecular mechanisms by which these channels contribute to neurodegeneration and their potential as therapeutic targets.
Connexin and Pannexin Family
Connexins
Connexins are a family of 21 members in humans, named by their molecular weight (e.g., Cx26 = 26 kDa). Key connexins in the CNS include: [@orellana2020]
Pannexins (PANX1, PANX2, PANX3) are a distinct family of channel proteins that primarily form single-membrane hemichannels rather than gap junction channels:
PANX1: Ubiquitously expressed, forms large-pore hemichannels (~500 Da cutoff)
PANX2: Primarily neuronal expression, forms smaller channels
PANX3: Expressed in skin, cartilage, and some glial cells
Channel Physiology
Gap Junction Channels
Gap junctions direct cell-to-cell communication by connecting the cytoplasm of adjacent cells:
Six connexins oligomerize to form a connexon (hemichannel)
Two connexons dock to form a gap junction channel
Each gap junction can contain homogeneous or heterogeneous connexons
Conductance: ~100 pS per channel, allowing ions and small molecules (<1 kDa)
Hemichannels
Unpaired hemichannels allow communication between intracellular and extracellular compartments:
Release of signaling molecules: ATP, glutamate, NAD+, prostaglandins
uptake of nutrients and ions: Calcium, sodium, potassium