Year: 2008
Type: article
Abstract: Alzheimer's disease (AD) is characterized by extensive neuronal death that causes progressive memory loss. Accumulation of Aβ aggregates and neurofibrillary tangles are believed to be responsible for AD-associated neurodegeneration. Aβ 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. 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. 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. This observation is completely new and might indicate targeting of severing proteins as a possible therapeutic strategy for AD.
Source: Alzheimer s & Dementia
Institution: Drexel University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2032742319