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• W2807458082 abstract "Prior studies in C. elegans demonstrated that the expression of aggregation-prone polyglutamine proteins in muscle wall cells compromised the folding of co-expressed temperature-sensitive proteins, prompting interest in whether the accumulation of a misfolded protein in pathologic features of human neurodegenerative disease burdens cellular proteostatic machinery in a manner that impairs the folding of other cellular proteins.Mice expressing high levels of mutant forms of tau and α-synuclein (αSyn), which develop inclusion pathologies of the mutant protein in brain and spinal cord, were crossed to mice expressing low levels of mutant superoxide dismutase 1 fused to yellow fluorescent protein (G85R-SOD1:YFP) for aging and neuropathological evaluation.Mice expressing low levels of G85R-SOD1:YFP, alone, lived normal lifespans and were free of evidence of inclusion pathology, setting the stage to use this protein as a reporter of proteostatic function. We observed robust induction of G85R-SOD1:YFP inclusion pathology in the neuropil of spinal cord and brainstem of bigenic mice that co-express high levels of mutant tau in the spinal axis and develop robust spinal tau pathology (JNPL3 mice). In contrast, in crosses of the G85R-SOD1:YFP mice with mice that model spinal α-synucleinopathy (the M83 model of αSyn pathology), we observed no G85R-SOD1:YFP inclusion formation. Similarly, in crosses of the G85R-SOD1:YFP mice to mice that model cortical tau pathology (rTg4510 mice), we did not observe induction of G85R-SOD1:YFP inclusions.Despite robust burdens of neurodegenerative pathology in M83 and rTg4510 mice, the introduction of the G85R-SOD1:YFP protein was induced to aggregate only in the context of spinal tau pathology present in the JNPL3 model. These findings suggest unexpected specificity, mediated by both the primary protein pathology and cellular context, in the induced secondary aggregation of a mutant form of SOD1 that could be viewed as a reporter of proteostatic function." @default.
• W2807458082 created "2018-06-13" @default.
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• W2807458082 date "2018-05-18" @default.
• W2807458082 modified "2023-10-18" @default.
• W2807458082 title "Differential induction of mutant SOD1 misfolding and aggregation by tau and α-synuclein pathology" @default.
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• W2807458082 doi "https://doi.org/10.1186/s13024-018-0253-9" @default.
• W2807458082 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5960184" @default.
• W2807458082 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29776378" @default.
• W2807458082 hasPublicationYear "2018" @default.
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