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Neurotoxic astrocytes express the D-serine synthesizing enzyme, serine racemase, in Alzheimer’s disease
- Source :
- Neurobiol Dis, Neurobiology of Disease, Vol 130, Iss, Pp 104511-(2019)
- Publication Year :
- 2019
-
Abstract
- Although β-amyloid plaques are a well-recognized hallmark of Alzheimer's disease (AD) neuropathology, no drugs reducing amyloid burden have shown efficacy in clinical trials, suggesting that once AD symptoms emerge, disease progression becomes independent of Aβ production. Reactive astrocytes are another neuropathological feature of AD, where there is an emergence of neurotoxic (A1) reactive astrocytes. We find that serine racemase (SR), the neuronal enzyme that produces the N-methyl-d-aspartate receptor (NMDAR) co-agonist d-serine, is robustly expressed in A1-reactive neurotoxic astrocytes in the hippocampus and entorhinal cortex of AD subjects and an AD rat model. Furthermore, we observe intracellular signaling changes consistent with increased extra-synaptic NMDAR activation, excitotoxicity and decreased neuronal survival. Thus, reducing neurotoxic d-serine release from A1 inflammatory astrocytes could have therapeutic benefit for mild to advanced AD, when anti-amyloid strategies are ineffective.
- Subjects :
- 0301 basic medicine
Excitotoxicity
Racemases and Epimerases
Hippocampus
Neuropathology
medicine.disease_cause
Glial fibrillary acidic protein
Article
lcsh:RC321-571
Serine
03 medical and health sciences
0302 clinical medicine
Alzheimer Disease
medicine
Animals
Entorhinal Cortex
Humans
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
biology
business.industry
Complement C3
Entorhinal cortex
Extrasynaptic
Rats
Disease Models, Animal
030104 developmental biology
Neurology
N-methyl-d-asparate receptor
Serine racemase
Astrocytes
biology.protein
NMDA receptor
Rats, Transgenic
business
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Neurobiol Dis, Neurobiology of Disease, Vol 130, Iss, Pp 104511-(2019)
- Accession number :
- edsair.doi.dedup.....858b5bff250d09a080bcb33c7a6148da