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REVIEW article

Front. Cell. Neurosci.
Sec. Cellular Neuropathology
Volume 19 - 2025 | doi: 10.3389/fncel.2025.1532960
This article is part of the Research Topic Intercellular communication in chronic neuroinflammatory diseases View all articles

Mechanistic insights into connexin-mediated neuroglia crosstalk in neurodegenerative diseases

Provisionally accepted

The final, formatted version of the article will be published soon.

    Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Multiple Sclerosis (MS), and Huntington’s disease (HD), although distinct in their clinical manifestations, share a common hallmark: a disrupted neuroinflammatory environment orchestrated by dysregulation of neuroglial intercellular communication. Neuroglial crosstalk is physiologically ensured by extracellular mediators and by the activity of connexins (Cxs), the forming proteins of gap junctions (Gjs) and hemichannels (HCs), which maintain intracellular and extracellular homeostasis. However, accumulating evidence suggests that Cxs can also act as pathological pore in neuroinflammatory conditions, thereby contributing to neurodegenerative phenomena such as synaptic dysfunction, oxidative stress, and ultimately cell death. This review explores mechanistic insights of Cxs-mediated intercellular communication in the progression of neurodegenerative diseases and discuss the therapeutic potential of targeting Cxs to restore cellular homeostasis.

    Keywords: Chronic neuroinflammation, neurodegeneration, Connexin 43, Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Huntington's disease

    Received: 22 Nov 2024; Accepted: 20 Jan 2025.

    Copyright: © 2025 Denaro, D'Aprile, Vicario and Parenti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Rosalba Parenti, University of Catania, Catania, Italy

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