Astrocytes in Neurodegenerative Disease: Table 1.

Phatnani, Hemali; Maniatis, Tom

doi:10.1101/cshperspect.a020628

Cited by 331 publications

(251 citation statements)

References 171 publications

(217 reference statements)

Supporting

Mentioning

245

Contrasting

Unclassified

Order By: Relevance

“…Both astrocytes and microglia have also been implicated in numerous neurological and psychiatric diseases (e.g. ALS, Alzheimer's disease and Parkinson's disease; Phatnani and Maniatis, 2015;Ginhoux and Prinz, 2015). In most cases, it is incompletely understood whether their contributions to these diseases are due to toxic gain of functions (e.g.…”

Section: Central Roles Of Glia In Injury Regeneration and Diseasementioning

confidence: 99%

Glia in mammalian development and disease

2015

View full text Add to dashboard Cite

Glia account for more than half of the cells in the mammalian nervous system, and the past few decades have witnessed a flood of studies that detail novel functions for glia in nervous system development, plasticity and disease. Here, and in the accompanying poster, we review the origins of glia and discuss their diverse roles during development, in the adult nervous system and in the context of disease.

show abstract

Section: Central Roles Of Glia In Injury Regeneration and Diseasementioning

confidence: 99%

Glia in mammalian development and disease

2015

View full text Add to dashboard Cite

show abstract

“…Furthermore, astrocytes store brain energy currency in the form of glycogen [7], and release substrates for neuronal oxidative phosphorylation [25]. Moreover, astrocytes have been suggested as contributors to neurodegenerative disorders by various mechanisms, including via metabolic dysfunction [27], making them potential targets for novel strategies to treat brain disorders. Given their importance for brain function, the generation of astrocytes from NSCs has attracted much attention recently.…”

Section: Introductionmentioning

confidence: 99%

Quantification of Metabolic Rearrangements During Neural Stem Cells Differentiation into Astrocytes by Metabolic Flux Analysis

et al. 2016

View full text Add to dashboard Cite

Proliferation and differentiation of neural stem cells (NSCs) have a crucial role to ensure neurogenesis and gliogenesis in the mammalian brain throughout life. As there is growing evidence for the significance of metabolism in regulating cell fate, knowledge on the metabolic programs in NSCs and how they evolve during differentiation into somatic cells may provide novel therapeutic approaches to address brain diseases. In this work, we applied a quantitative analysis to assess how the central carbon metabolism evolves upon differentiation of NSCs into astrocytes. Murine embryonic stem cell (mESC)-derived NSCs and astrocytes were incubated with labelled [1-13 C]glucose and the label incorporation into intracellular metabolites was followed by GC-MS. The obtained 13 C labelling patterns, together with uptake/secretion rates determined from supernatant analysis, were integrated into an isotopic non-stationary metabolic flux analysis ( 13 C-MFA) model to estimate intracellular flux maps. Significant metabolic differences between NSCs and astrocytes were identified, with a general downregulation of central carbon metabolism during astrocytic differentiation. While glucose uptake was 1.7-fold higher in NSCs (on a per cell basis), a high lactate-secreting phenotype was common to both cell types. Furthermore, NSCs consumed glutamine from the medium; the highly active reductive carboxylation of alpha-ketoglutarate indicates that this was converted to citrate and used for biosynthetic purposes. In astrocytes, pyruvate entered the TCA cycle mostly through pyruvate carboxylase (81%). This pathway supported glutamine and citrate secretion, recapitulating well described metabolic features of these cells in vivo. Overall, this fluxomics study allowed us to quantify the metabolic rewiring accompanying astrocytic lineage specification from NSCs.

show abstract

“…In most cases, astrocytes become transiently hypertrophic and express high levels of intermediate filament proteins such as glial fibrillary acid protein (GFAP) 3 and vimentin (4,5). In cases of severe damage, astrocyte proliferation increases, causing scar formation (6,7).…”

mentioning

confidence: 99%

“…Reactive astrogliosis occurs in response to all forms of CNS insults including trauma, infections, stroke, neurodegeneration, and epilepsy (1)(2)(3). In most cases, astrocytes become transiently hypertrophic and express high levels of intermediate filament proteins such as glial fibrillary acid protein (GFAP) 3 and vimentin (4,5).…”

mentioning

confidence: 99%

Neuronal mTORC1 Is Required for Maintaining the Nonreactive State of Astrocytes

Zhang

Liang

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by F. Anne StephensonAstrocytes respond to CNS insults through reactive astrogliosis, but the underlying mechanisms are unclear. In this study, we show that inactivation of mechanistic target of rapamycin complex (mTORC1) signaling in postnatal neurons induces reactive astrogliosis in mice. Ablation of Raptor (an mTORC1-specific component) in postmitotic neurons abolished mTORC1 activity and produced neurons with smaller soma and fewer dendrites, resulting in microcephaly and aberrant behavior in adult mice. Interestingly, extensive astrogliosis without significant astrocyte proliferation and glial scar formation was observed in these mice. The inhibition of neuronal mTORC1 may activate astrogliosis by reducing neuron-derived fibroblast growth factor 2 (FGF-2), which might trigger FGF receptor signaling in astrocytes to maintain their nonreactive state, and FGF-2 injection successfully prevented astrogliosis in Raptor knock-out mice. This study demonstrates that neuronal mTORC1 inhibits reactive astrogliosis and plays an important role in CNS pathologies.

show abstract

Astrocytes in Neurodegenerative Disease: Table 1.

Cited by 331 publications

References 171 publications

Glia in mammalian development and disease

Glia in mammalian development and disease

Quantification of Metabolic Rearrangements During Neural Stem Cells Differentiation into Astrocytes by Metabolic Flux Analysis

Neuronal mTORC1 Is Required for Maintaining the Nonreactive State of Astrocytes

Contact Info

Product

Resources

About