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A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD
Identification of a Unique TGF-β Dependent Molecular and Functional Signature in Microglia
- O. Butovsky, Mark P. Jedrychowski, +15 authors H. Weiner
- Medicine, BiologyNature Neuroscience
- 8 December 2013
It is found that TGF-β was required for the in vitro development of microglia that express the microglial molecular signature characteristic of adultmicroglia and that microglian were absent in the CNS of TGF -β1–deficient mice.
Knockout of Glutamate Transporters Reveals a Major Role for Astroglial Transport in Excitotoxicity and Clearance of Glutamate
Localization of neuronal and glial glutamate transporters
Oligodendroglia metabolically support axons and contribute to neurodegeneration
It is shown that the most abundant lactate transporter in the central nervous system, monocarboxylate transporter 1 (MCT1, also known as SLC16A1), is highly enriched within oligodendroglia and that disruption of this transporter produces axon damage and neuron loss in animal and cell culture models.
β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression
Using a blinded screen of 1,040 FDA-approved drugs and nutritionals, it is discovered that many β-lactam antibiotics are potent stimulators of GLT1 expression, and this action appears to be mediated through increased transcription of theGLT1 gene.
From charcot to lou gehrig: deciphering selective motor neuron death in als
Insights into abnormalities in two genes, together with errors in the handling of synaptic glutamate and the potential excitotoxic response that this alteration provokes, have provided leads for the development of new strategies to identify an as yet elusive remedy for this progressive, fatal disorder.
Selective loss of glial glutamate transporter GLT‐1 in amyotrophic lateral sclerosis
- J. Rothstein, M. van Kammen, A. Levey, Lee J Martin, R. Kuncl
- Biology, MedicineAnnals of neurology
- 1 July 1995
Developing C‐terminal, antioligopeptide antibodies that were specific for each glutamate transporter subtype found that GLT‐1 immunoreactive protein was severely decreased in ALS, both in motor cortex (71% decrease compared with control) and in spinal cord.
C9orf72 Nucleotide Repeat Structures Initiate Molecular Cascades of Disease
It is demonstrated that distinct C9orf72 HRE structural polymorphism at both DNA and RNA levels initiates molecular cascades leading to ALS/FTD pathologies, and provides the basis for a mechanistic model for repeat-associated neurodegenerative diseases.
Glutamate Transporter Protein Subtypes Are Expressed Differentially during Rat CNS Development
It is concluded that during CNS development the expression of glutamate transporter subtypes is differentially regulated, regionally segregated, and coordinated.