Apoptosis in Transgenic Mice Expressing the P301L Mutated Form of Human Tau
| Autor: | Cecília M. P. Rodrigues, Rui E. Castro, Rita M. Ramalho, Ricardo J.S. Viana, Walter C. Low, Clifford J. Steer |
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| Přispěvatelé: | Repositório da Universidade de Lisboa |
| Rok vydání: | 2008 |
| Předmět: |
Genetically modified mouse
Biochemistry & Molecular Biology Transgene Immunoblotting Apoptosis Mice Transgenic tau Proteins Cleavage (embryo) Hippocampus Mice chemistry.chemical_compound In Situ Nick-End Labeling Genetics medicine Animals Humans Rats Wistar Molecular Biology Cells Cultured Research Articles Genetics (clinical) Cerebral Cortex Neurons Caspase 3 Neurodegeneration Tauroursodeoxycholic acid Cell Biology medicine.disease Immunohistochemistry Rats Cell biology Medicine Research & Experimental Amino Acid Substitution chemistry Mutation Molecular Medicine DNA fragmentation Tauopathy |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| ISSN: | 1528-3658 1076-1551 |
| Popis: | The rTg4510 mouse is a tauopathy model, characterized by massive neurodegeneration in Alzheimer's disease (AD)-relevant cortical and limbic structures, deficits in spatial reference memory, and progression of neurofibrillary tangles (NFT). In this study, we examined the role of apoptosis in neuronal loss and associated tau pathology. The results showed that DNA fragmentation and caspase-3 activation are common in the hippocampus and frontal cortex of young rTg4510 mice, These changes were associated with cleavage of tau into smaller intermediate fragments, which persist with age. Interestingly, active caspase-3 was off en co-localized with cleaved tau. In vitro, fibrillar A beta(1-42) resulted in nuclear fragmentation, caspase activation, and caspase-3-induced cleavage of tau. Notably, incubation with the antiapoptotic molecule tauroursodeoxycholic acid abrogated apoptosis-mediated cleavage of tau in rat cortical neurons. In conclusion, caspase-3-cleaved intermediate tau species occurred early in rTg54510 brains and preceded cell loss in A beta-exposed cultured neurons. These results suggest a potential role of apoptosis in neurodegeneration. |
| Databáze: | OpenAIRE |
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