Astroglial Connexins in Neurodegenerative Diseases

Huang, Xiaomin; Su, Yixun; Wang, Nan; Li, Hui; Li, Zhigang; Yin, Guowei; Chen, Hui; Niu, Jianqin; Yi, Chenju

doi:10.3389/fnmol.2021.657514

Cited by 33 publications

(24 citation statements)

References 111 publications

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“…Increased Cx43-immunostaining in cortical regions containing b-amyloid plaques has been reported in Alzheimer's disease (AD) [41] and increased Cx43 density has been reported in the caudate nucleus in Huntington's disease (HD) [42]. Altered Cx43 expression has also been reported in Parkinson's disease (PD), amyotrophic lateral sclerosis and demyelinating disorders [5,39,43]. A recent study in cases with ageing-related tau astrogliopathy (ARTAG) found an increase in Cx43 density that correlated with the density of tau pathology [36].…”

Section: Discussionmentioning

confidence: 99%

Distribution patterns of astrocyte populations in the human cortex

Forrest

Kim

Crockford

et al. 2022

Preprint

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Astrocytes are a major class of glial cell in the central nervous system that have a diverse range of types and functions thought to be based on their anatomical location, morphology and cellular properties. Recent studies highlight that astrocyte dysfunction contributes to the pathogenesis of neurological conditions. However, few studies have described the pattern, distribution and density of astrocytes in the adult human cortex. This study mapped the distribution and density of astrocytes immunolabelled with a range of cytoskeletal and membrane markers in the human frontal cortex. Distinct and overlapping astrocyte populations were determined. The frontal cortex from ten normal control cases (75±9 years) was immunostained with glial fibrillary acidic protein (GFAP), aldehyde dehydrogenase-1 L1 (ALDH1L1), connexin-43 (Cx43), aquaporin-4 (AQP4), and glutamate transporter 1 (GLT-1). All markers labelled populations of astrocytes in the grey and white matter, separate cortical layers, subpial and perivascular regions. All markers were informative for labelling different cellular properties and cellular compartments of astrocytes. ALDH1L1 labelled the largest population of astrocytes, and Cx43-immunopositive astrocytes were found in all cortical layers. AQP4 and GLT-1 labelled distal astrocytic process and end-feet in the same population of astrocytes (98% of GLT-1-immunopositive astrocytes contained AQP4). This study highlights the diversity of astrocytes in the human cortex, providing a reference map of the distribution of distinct and overlapping astrocyte populations which can be used for comparative purposes in various disease, inflammatory and injury states involving astrocytes.

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Section: Discussionmentioning

confidence: 99%

Distribution patterns of astrocyte populations in the human cortex

Forrest

Kim

Crockford

et al. 2022

Preprint

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“…Changes in connexin’s abundance, distribution, posttranslational modifications and degradation are known to play an important pathophysiological role in several conditions and organs, particularly in the heart and the brain ( Rodríguez-Sinovas et al, 2012 ; Huang et al, 2021 ; Rodríguez-Sinovas et al, 2021 ; Tittarelli, 2021 ). The specific role of mitochondrial connexins in these contexts is less known.…”

Section: Pathophysiological Relevance Of Mitochondrial Connexinsmentioning

confidence: 99%

Connexin 43 in Mitochondria: What Do We Really Know About Its Function?

et al. 2022

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Connexins are known for their ability to mediate cell-cell communication via gap junctions and also form hemichannels that pass ions and molecules over the plasma membrane when open. Connexins have also been detected within mitochondria, with mitochondrial connexin 43 (Cx43) being the best studied to date. In this review, we discuss evidence for Cx43 presence in mitochondria of cell lines, primary cells and organs and summarize data on its localization, import and phosphorylation status. We further highlight the influence of Cx43 on mitochondrial function in terms of respiration, opening of the mitochondrial permeability transition pore and formation of reactive oxygen species, and also address the presence of a truncated form of Cx43 termed Gja1-20k. Finally, the role of mitochondrial Cx43 in pathological conditions, particularly in the heart, is discussed.

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“…Likewise, the enhanced expression of astrocytic Cx43 is altered in animal models of ALS and PD [175]. As in AD, the high expression of Cx43 is hypothesized to cause excessive release of ATP or glutamate into the extracellular space [175], ultimately leading or contributing to neurodegeneration [176]. Thus, there are many shared features in astrocyte-neuronal communication changes in diverse types of neurodegenerative diseases that may be a consequence of the astrocytic responses to their reactive state.…”

Section: Changes To Gliotransmission In Neurodegenerative Diseases Other Than Admentioning

confidence: 99%

Dysregulation of Astrocyte–Neuronal Communication in Alzheimer’s Disease

Nanclares

Baraibar

Araque

et al. 2021

IJMS

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Recent studies implicate astrocytes in Alzheimer’s disease (AD); however, their role in pathogenesis is poorly understood. Astrocytes have well-established functions in supportive functions such as extracellular ionic homeostasis, structural support, and neurovascular coupling. However, emerging research on astrocytic function in the healthy brain also indicates their role in regulating synaptic plasticity and neuronal excitability via the release of neuroactive substances named gliotransmitters. Here, we review how this “active” role of astrocytes at synapses could contribute to synaptic and neuronal network dysfunction and cognitive impairment in AD.

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Astroglial Connexins in Neurodegenerative Diseases

Cited by 33 publications

References 111 publications

Distribution patterns of astrocyte populations in the human cortex

Distribution patterns of astrocyte populations in the human cortex

Connexin 43 in Mitochondria: What Do We Really Know About Its Function?

Dysregulation of Astrocyte–Neuronal Communication in Alzheimer’s Disease

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