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P4‐278: Microtubule severing protein expression in Alzheimer's disease animal models
Author(s) -
Ansaloni Sara,
Nichols Robert,
Baas Peter W.,
Saunders Aleister J.
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.2347
Subject(s) - neurodegeneration , tau protein , microtubule , microbiology and biotechnology , genetically modified mouse , transgene , cytoskeleton , biology , microtubule associated protein , chemistry , neuroscience , alzheimer's disease , biochemistry , pathology , medicine , disease , cell , gene
Background: Alzheimer’s disease (AD) is characterized by extensive neuronal death that causes progressive memory loss. Accumulation of A aggregates and neurofibrillary tangles are believed to be responsible for AD-associated neurodegeneration. A is a toxic peptide generated by the enzymatic cleavage of APP which can aggregate inside or outside the neurons. Neurofibrillary tangles are formed when the Tau protein, a microtubule (MT) associated protein, is hyper-phosphorylated. Hyper-phosphorylated Tau cannot bind MTs. Failure of Tau binding to MTs causes destabilization by increased de-polymerization. Potentially, Tau-deprived MTs are also more accessible to severing proteins. In fact, Tau has been shown to protect MTs from severing by katanin and spastin. Methods: We hypothesize that levels of katanin and spastin might differ between control and transgenic mouse models of AD. To test this hypothesis we performed Western Blot analysis of cortex and hippocampus tissue isolated from transgenic and control mice. Results: We found that katanin levels are decreased in triple transgenic animals. Regulation of katanin levels might be a defense mechanism to avoid further cytoskeleton degeneration. Conclusions: This observation is completely new and might indicate targeting of severing proteins as a possible therapeutic strategy for AD.