Mechanisms of Disease: astrocytes in neurodegenerative disease

@article{Maragakis2006MechanismsOD,
  title={Mechanisms of Disease: astrocytes in neurodegenerative disease},
  author={Nicholas J. Maragakis and Jeffrey D. Rothstein},
  journal={Nature Clinical Practice Neurology},
  year={2006},
  volume={2},
  pages={679-689}
}
The term neurodegenerative disease refers to the principal pathology associated with disorders such as amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease and Parkinson's disease, and it is presumed that neurodegeneration results in the clinical findings seen in patients with these diseases. Decades of pathological and physiological studies have focused on neuronal abnormalities in these disorders, but it is becoming increasingly evident that astrocytes are also important… 
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References

SHOWING 1-10 OF 82 REFERENCES
Cellular pathology of Parkinson’s disease: astrocytes, microglia and inflammation
TLDR
The different aspects of activated glial cells and potential mechanisms that mediate or protect against cell loss in PD are discussed.
Impaired Glutamate Transport in a Mouse Model of Tau Pathology in Astrocytes
TLDR
A transgenic mouse model of tau pathology in astrocytes is generated by expressing the human tau protein under the control of the glial fibrillary acidic protein (GFAP) promoter and it is demonstrated that compromised motor function and deficits in neuromuscular strength are observed that correlates with reduced expression of glutamate transporter-1 and occurs concurrent with tau inclusion pathology.
Impaired Glutamate Uptake in the R6 Huntington's Disease Transgenic Mice
TLDR
It is shown that a decreased mRNA level of the major astroglial glutamate transporter (GLT1) in the striatum and cortex of these mice is accompanied by a concomitant decrease in glutamate uptake, suggesting that a defect in astrocytic glutamate uptake may contribute to the phenotype and neuronal cell death in HD.
Widespread cytoskeletal pathology characterizes corticobasal degeneration.
TLDR
It is demonstrated that the nonamyloid cortical plaques of CBD are actually collections of abnormal tau in the distal processes of astrocytes, which refines the diagnosis and pathophysiological understanding of this unique disease and has important implications for other neurodegenerative diseases, like Alzheimer's disease.
Transgenic Mouse Model of Tau Pathology in Astrocytes Leading to Nervous System Degeneration
TLDR
The transgenic Tg mice recapitulate key features of astrocytic pathology observed in human tauopathies and demonstrate functional consequences of this pathology including neuron degeneration in the absence of neuronal tau inclusions.
Amyotrophic Lateral Sclerosis: Pathogenesis, Differential Diagnoses, And Potential Interventions
TLDR
Findings are inconclusive, and further investigations are underway, but at present, nonpharmacologic interventions such as nutritional support; physical, speech, and occupational therapy; and respiratory management offer the best means of improving quality of life for patients with ALS.
Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis.
TLDR
ALS is associated with a defect in high-affinity glutamate transport that has disease, region, and chemical specificity and could lead to neurotoxic levels of extracellular glutamate and thus be pathogenic in ALS.
...
...