Astrocyte signaling and neurodegeneration

Brambilla, Liliana; Martorana, Francesca; Rossi, Daniela

doi:10.4161/pri.22512

Cited by 55 publications

(31 citation statements)

References 143 publications

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“…During forebrain development, neural stem cells generate neurons first, followed by astrocytes, and finally oligodendrocytes. This temporal sequence of neocortex development is tightly regulated by both intrinsic programs and extracellular signals (Brambilla et al, 2013). Astrocytes originate from progenitor cells in the subventricular zone (SVZ) during late embryonic development and reach a peak level in early postnatal life (Sauvageot, 2002).…”

Section: Introductionmentioning

confidence: 99%

DISC1 regulates astrogenesis in the embryonic brain via modulation of RAS/MEK/ERK signaling through RASSF7

et al. 2016

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Disrupted in schizophrenia 1 (DISC1) is known as a high susceptibility gene for schizophrenia. Recent studies have indicated that schizophrenia might be caused by glia defects and dysfunction. However, there is no direct evidence of a link between the schizophrenia gene DISC1 and gliogenesis defects. Thus, an investigation into the involvement of DISC1 (a ubiquitously expressed brain protein) in astrogenesis during the late stage of mouse embryonic brain development is warranted. Here, we show that suppression of DISC1 expression represses astrogenesis in vitro and in vivo, and that DISC1 overexpression substantially enhances the process. Furthermore, mouse and human DISC1 overexpression rescued the astrogenesis defects caused by DISC1 knockdown. Mechanistically, DISC1 activates the RAS/MEK/ERK signaling pathway via direct association with RASSF7. Also, the pERK complex undergoes nuclear translocation and influences the expression of genes related to astrogenesis. In summary, our results demonstrate that DISC1 regulates astrogenesis by modulating RAS/MEK/ERK signaling via RASSF7 and provide a framework for understanding how DISC1 dysfunction might lead to neuropsychiatric diseases.

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Section: Introductionmentioning

confidence: 99%

DISC1 regulates astrogenesis in the embryonic brain via modulation of RAS/MEK/ERK signaling through RASSF7

et al. 2016

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“…Mounting evidence suggest that local inflammatory responses are mediated by astrocytes and that these astrocytes are not simply passive supportive cells, but contribute to the pathological processes of neurodegenerative diseases (Zaheer et al, 2012) and precede neuronal alterations and behavioral impairment in the progression of AD (Brambilla et al, 2012). Epidemiological studies suggest that saturated free fatty acids may increase the risk of AD (Takechi et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

P3–076: Palmitate induces transcriptional regulation of BACE1 and presenilin by STAT3 in neurons mediated by astrocytes

Liu

Martin

Kohler

et al. 2013

Alzheimer's & Dementia

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Deregulation of calcium has been implicated in neurodegenerative diseases, including Alzheimer's disease (AD). Previously, we showed that saturated free-fatty acid, palmitate, causes AD-like changes in primary cortical neurons mediated by astrocytes. However, the molecular mechanisms by which conditioned media from astrocytes cultured in palmitate induces AD-like changes in neurons are unknown. This study demonstrates that this condition media from astrocytes elevates calcium level in the neurons, which subsequently increases calpain activity, a calcium-dependent protease, leading to enhance p25/Cdk5 activity and phosphorylation and activation of the STAT3 (signal transducer and activator of transcription) transcription factor. Inhibiting calpain or Cdk5 significantly reduces the upregulation in nuclear level of pSTAT3, which we found to transcriptionally regulate both BACE1 and presenilin-1, the latter is a catalytic subunit ofsecretase. Decreasing pSTAT3 levels reduced the mRNA levels of both BACE1 and presenilin-1 to near control levels. These data demonstrate a signal pathway leading to the activation of STAT3, and the generation of the amyloid peptide. Thus, our results suggest that STAT3 is an important potential therapeutic target of AD pathogenesis.

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“…154 These Ca 2+ variations appear critical for the release of neurotoxic concentrations of the gliotransmitter glutamate, and the regulation of astrocyte signaling glutamate receptors and ATP-activated purigenic receptors (P 2 Y 1 ). 154 The importance of glutamate toxicity in astrocytes is emphasized by the chronically activated glial cells that surround depositions of PrP Sc in prion disease evoked by fragments (106-126). 152,154 There is currently no information on the Ca 2+ signaling of scrapie-infected astroglia.…”

Section: Presynaptic Sidementioning

confidence: 99%

“…154 The importance of glutamate toxicity in astrocytes is emphasized by the chronically activated glial cells that surround depositions of PrP Sc in prion disease evoked by fragments (106-126). 152,154 There is currently no information on the Ca 2+ signaling of scrapie-infected astroglia. 154 Dysregulation of the GSH antioxidant cascade initiated by PrP C increases neural sensitivity.…”

Section: Presynaptic Sidementioning

confidence: 99%

“…152,154 There is currently no information on the Ca 2+ signaling of scrapie-infected astroglia. 154 Dysregulation of the GSH antioxidant cascade initiated by PrP C increases neural sensitivity. 73 If astrocytic glial glutamate transporter 1 (GLT1) is impaired, there will be a build-up of glutamate in synaptic clefts and a resultant neural hyperexcitability and hyperalgesia.…”

Section: Presynaptic Sidementioning

confidence: 99%

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Prion Protein Signaling in the Nervous System—A Review and Perspective

Liebert

Bicknell

Adams³

2014

Signal Transduction Insights

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Prion protein (PrP C ) was originally known as the causative agent of transmissible spongiform encephalopathy (TSE) but with recent research, its true function in cells is becoming clearer. It is known to act as a scaffolding protein, binding multiple ligands at the cell membrane and to be involved in signal transduction, passing information from the extracellular matrix (ECM) to the cytoplasm. Its role in the coordination of transmitters at the synapse, glyapse, and gap junction and in short-and long-range neurotrophic signaling gives PrP C a major part in neural transmission and nervous system signaling. It acts to regulate cellular function in multiple targets through its role as a controller of redox status and calcium ion flux.

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Astrocyte signaling and neurodegeneration

Cited by 55 publications

References 143 publications

DISC1 regulates astrogenesis in the embryonic brain via modulation of RAS/MEK/ERK signaling through RASSF7

DISC1 regulates astrogenesis in the embryonic brain via modulation of RAS/MEK/ERK signaling through RASSF7

P3–076: Palmitate induces transcriptional regulation of BACE1 and presenilin by STAT3 in neurons mediated by astrocytes

Prion Protein Signaling in the Nervous System—A Review and Perspective

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