Methylene blue fails to inhibit Tau and polyglutamine protein dependent toxicity in zebrafish
| Autor: | Alexander Hruscha, Dominik Paquet, Frauke van Bebber, Christian Haass, Bettina Schmid |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Huntingtin
Fluorescent Antibody Technique Animals Genetically Modified chemistry.chemical_compound 0302 clinical medicine metabolism [Peptides] metabolism [Zebrafish] Phosphorylation Cognitive decline drug effects [Axons] pharmacology [Methylene Blue] Zebrafish Neurons 0303 health sciences Cell Death biology Neurodegeneration Huntington's disease Alzheimer's disease 3. Good health Tauopathies Neurology Biochemistry metabolism [Neurons] Frontotemporal dementia Methylene blue Amyloid Neurite Blotting Western tau Proteins lcsh:RC321-571 03 medical and health sciences metabolism [Animals Genetically Modified] genetics [Peptides] drug effects [Phosphorylation] ddc:570 mental disorders medicine drug effects [Neurons] Animals lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry 030304 developmental biology genetics [Zebrafish] genetics [Tauopathies] Neurotoxicity drug effects [Cell Death] medicine.disease biology.organism_classification metabolism [tau Proteins] Axons Methylene Blue genetics [tau Proteins] chemistry metabolism [Tauopathies] Peptides polyglutamine 030217 neurology & neurosurgery |
| Zdroj: | Neurobiology of Disease; Vol 39 Neurobiology of disease 39(3), 265-271 (2010). doi:10.1016/j.nbd.2010.03.023 Neurobiology of Disease, Vol 39, Iss 3, Pp 265-271 (2010) |
| ISSN: | 0969-9961 |
| Popis: | Methylene blue is an FDA approved compound with a variety of pharmacologic activities. It inhibits aggregation of several amyloidogenic proteins known to be deposited in neurodegenerative diseases. Recently, it has been proposed that methylene blue shows significant beneficial effects in a phase 2 clinical trial by slowing cognitive decline in Alzheimer's disease patients. To analyze its therapeutic potential, we investigated the effect of methylene blue on neurotoxicity in a zebrafish model for tauopathies. Transgenic expression of the frontotemporal dementia associated Tau-P301L mutation recapitulates a number of the pathological features observed in humans including abnormal phosphorylation and folding of Tau, tangle formation and Tau dependent neuronal loss. Upon incubation of zebrafish larvae with methylene blue, neither abnormal phosphorylation nor neuronal cell loss, reduced neurite outgrowth or a swimming defect were rescued. Methylene blue is biologically active in zebrafish since it reduced aggregation of a huntingtin variant containing a stretch of 102 glutamine residues. However, although huntingtin aggregation was largely prevented by methylene blue, huntingtin-dependent toxicity was unaffected. Our findings are consistent with the hypothesis that toxicity is not necessarily associated with deposition of insoluble amyloid proteins. |
| Databáze: | OpenAIRE |
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