[DOWNLOAD] "Clarification of Tau Fibrillization Pathway in Vitro Implications to Alzheimer’s Disease" by Carmen Nicoleta Chirita * Book PDF Kindle ePub Free
eBook details
- Title: Clarification of Tau Fibrillization Pathway in Vitro Implications to Alzheimer’s Disease
- Author : Carmen Nicoleta Chirita
- Release Date : January 18, 2013
- Genre: Medical,Books,Professional & Technical,
- Pages : * pages
- Size : 18609 KB
Description
In vitro tau polymerization in the presence of inducers is a good model for the fibrillization of the protein in Alzheimer’s disease, a process believed to lead to neurodegeneration. Here we characterize the mechanism of tau polymerization induction by free fatty acids and newly identified inducers (anionic surfactants and microspheres and dyes). We show that detergent micelles and phospholipid vesicles nucleate filament formation and this parallels observations from biopsy samples of Alzheimer’s disease patients. We parallel these results with another natively unstructured amyloid forming protein, α-synuclein, and with a homologous microtubule associated protein, MAP2c. Finally, we show that tau polymerization proceeds via a partially folded assembly intermediate and that dye molecules can modulate tau polymerization, by affecting the propensity or the nature of this intermediate. The latter observation has relevance for the therapeutics of Alzheimer’s disease. Drugs that affect tau polymerization in certain ways can be tested for their efficiency and the pathogenicity of the intermediate versus the filament can be assessed.