Mechanistic insights into connexin-mediated neuroglia crosstalk in neurodegenerative diseases

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 neur...

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Main Authors: Simona Denaro, Simona D’Aprile, Nunzio Vicario, Rosalba Parenti
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fncel.2025.1532960/full
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author Simona Denaro
Simona D’Aprile
Nunzio Vicario
Rosalba Parenti
author_facet Simona Denaro
Simona D’Aprile
Nunzio Vicario
Rosalba Parenti
author_sort Simona Denaro
collection DOAJ
description 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 discusses the therapeutic potential of targeting Cxs to restore cellular homeostasis.
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institution Kabale University
issn 1662-5102
language English
publishDate 2025-02-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Cellular Neuroscience
spelling doaj-art-1247038dc63341acafe32165d9b6c70f2025-02-11T06:59:18ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022025-02-011910.3389/fncel.2025.15329601532960Mechanistic insights into connexin-mediated neuroglia crosstalk in neurodegenerative diseasesSimona DenaroSimona D’AprileNunzio VicarioRosalba ParentiNeurodegenerative 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 discusses the therapeutic potential of targeting Cxs to restore cellular homeostasis.https://www.frontiersin.org/articles/10.3389/fncel.2025.1532960/fullchronic neuroinflammationneurodegenerationconnexin 43Alzheimer’s diseaseParkinson’s diseasemultiple sclerosis
spellingShingle Simona Denaro
Simona D’Aprile
Nunzio Vicario
Rosalba Parenti
Mechanistic insights into connexin-mediated neuroglia crosstalk in neurodegenerative diseases
Frontiers in Cellular Neuroscience
chronic neuroinflammation
neurodegeneration
connexin 43
Alzheimer’s disease
Parkinson’s disease
multiple sclerosis
title Mechanistic insights into connexin-mediated neuroglia crosstalk in neurodegenerative diseases
title_full Mechanistic insights into connexin-mediated neuroglia crosstalk in neurodegenerative diseases
title_fullStr Mechanistic insights into connexin-mediated neuroglia crosstalk in neurodegenerative diseases
title_full_unstemmed Mechanistic insights into connexin-mediated neuroglia crosstalk in neurodegenerative diseases
title_short Mechanistic insights into connexin-mediated neuroglia crosstalk in neurodegenerative diseases
title_sort mechanistic insights into connexin mediated neuroglia crosstalk in neurodegenerative diseases
topic chronic neuroinflammation
neurodegeneration
connexin 43
Alzheimer’s disease
Parkinson’s disease
multiple sclerosis
url https://www.frontiersin.org/articles/10.3389/fncel.2025.1532960/full
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AT simonadaprile mechanisticinsightsintoconnexinmediatedneurogliacrosstalkinneurodegenerativediseases
AT nunziovicario mechanisticinsightsintoconnexinmediatedneurogliacrosstalkinneurodegenerativediseases
AT rosalbaparenti mechanisticinsightsintoconnexinmediatedneurogliacrosstalkinneurodegenerativediseases