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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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2025-02-01
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Series: | Frontiers in Cellular Neuroscience |
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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. |
format | Article |
id | doaj-art-1247038dc63341acafe32165d9b6c70f |
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 |
work_keys_str_mv | AT simonadenaro mechanisticinsightsintoconnexinmediatedneurogliacrosstalkinneurodegenerativediseases AT simonadaprile mechanisticinsightsintoconnexinmediatedneurogliacrosstalkinneurodegenerativediseases AT nunziovicario mechanisticinsightsintoconnexinmediatedneurogliacrosstalkinneurodegenerativediseases AT rosalbaparenti mechanisticinsightsintoconnexinmediatedneurogliacrosstalkinneurodegenerativediseases |