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The unique developmental and aging profile of tau protein in the long‐lived naked mole‐rat brain resists Aβ toxicity (728.8)
Author(s) -
Orr Miranda,
Salinas Angelica,
Buffenstein Rochelle
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.728.8
Subject(s) - neurodegeneration , phosphorylation , tau protein , tauopathy , biology , genetically modified mouse , transgene , microtubule , microbiology and biotechnology , alternative splicing , alzheimer's disease , neuroscience , biochemistry , messenger rna , medicine , gene , disease
Alzheimer’s disease (AD), the most prominent neurodegenerative disease, is characterized by Aß plaques, hyperphosphorylated tau, neurodegeneration and dementia. A prominent hypothesis suggests that elevated Aß peptide initiates AD pathogenesis including tau pathology. The tau protein, encoded by microtubule associated protein tau (MAPT) gene, is expressed predominantly in neuronal axons where it physiologically stabilizes microtubules (MTs). With over 20% of residues permissive to phosphorylation, tau function greatly depends on its phosphorylation state. Specifically, heavily phosphorylated tau loses MT binding affinity and coincides with neurodegeneration in AD. Unfortunately, genetically modified animal models overexpressing transgenic Aß have failed to recapitulate AD‐like tau misprocessing. To determine, instead, if endogenously expressed high levels of Aß alter tau and induce AD‐like pathology, we are studying the extremely long‐lived naked mole‐rat (NMR). NMRs, unlike mice, naturally contain measurable amounts of brain Aß. Using histological and biochemical assays, we have characterized tau protein from postnatal day 1 through 30 years of age. Remarkably, NMR brains display tau expression, phosphorylation, and splicing patterns distinct from mice and humans that seemingly enable them to cope with life‐long high levels of Aß. Grant Funding Source : Supported by: Biology of Aging Training Program 5T32AG021890