Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Turano, E; Busetto, G; Marconi, S; Guzzo, F; Farinazzo, A; Commisso, M; Bistaffa, E; Angiari, S; Musumeci, S; Sotgiu, S; Bonetti, B.
Neurotoxicity and synaptic plasticity impairment of N-acetylglucosamine polymers: implications for Alzheimer's disease.
Neurobiol Aging. 2015; 36(5): 1780-1791.
Doi: 10.1016/j.neurobiolaging.2014.12.033
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Angiari Stefano
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- Abstract:
- We assessed whether polymers of N-acetylglucosamine (GlcNAc) have any pathogenetic role in Alzheimer's disease (AD). First, by using specific dyes, we found deposits of polymers of GlcNAc in sporadic but not in familial AD. We found that neurons and microglia exposed to GlcNAc and uridine diphosphate (UDP)-GlcNAc are able to form GlcNAc polymers, which display a significant neurotoxicity in vitro. Moreover, the exposure of organotypic hippocampal cultures to the same compounds led to synaptic impairment with decreased levels of syntaxin and synaptophysin. In addition, acute hippocampal slices treated with GlcNAc/UDP-GlcNAc showed a clear reduction of long-term potentiation of excitatory synapses. Finally, we demonstrated that microglial cells are able to phagocytose chitin particles and, when exposed to GlcNAc/UDP-GlcNAc, show cellular activation and intracellular deposition of GlcNAc polymers that are eventually released in the extracellular space. Taken together, our results indicate that both microglia and neurons produce GlcNAc polymers, which trigger neurotoxicity both directly and through microglia activation. GlcNAc polymer-driven neurotoxicity offers novel pathogenic insights in sporadic AD and new therapeutic options. Copyright © 2015 Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Acetylglucosamine - metabolism
- Acetylglucosamine - toxicity
- Aged -
- Aged, 80 and over -
- Alzheimer Disease - etiology
- Animals -
- Cells, Cultured -
- Female -
- Hippocampus - cytology
- Humans -
- Long-Term Potentiation - drug effects
- Male -
- Mice -
- Microglia - metabolism
- Middle Aged -
- Neuronal Plasticity - drug effects
- Neurons - metabolism
- Polymers -
- Qa-SNARE Proteins - metabolism
- Synaptophysin - metabolism
- Find related publications in this database (Keywords)
- Alzheimer's disease
- N-acetylglucosamine
- Amyloid
- Neurotoxicity
- LTP