The Tau protein is of interest due to its structural role in neuronal cells and because its malfunction is associated with its self-association into toxic aggregates, leading to neurodegenerative diseases such as Alzheimer's disease and dementia [1]. Given the current state of knowledge on Tau biochemistry, the development of drug targets for treatment of Alzheimer's disease and dementia remains a challenge. There are over 70 potential drugs on the market targeting aggregation of peptides or proteins but may exhibit side-effects or cross-reactivity [2]. The main cause of neurodegeneration is aging, which is unavoidable. However, targeting Tau's role in Alzheimer's disease and dementia may promote significantly favorable outcomes and lead to development of improved therapeutic targets. Conversely, there are no conclusive studies on the pathway of Tau aggregation, early prevention of preformed fibrils, or complete treatment of these neurodegenerative diseases. With the use of the longest isoform of the Tau protein (Tau441), different spectroscopic and microscopic methods incorporating Tau441 and antibodies (monoclonal and polyclonal) were performed to unravel the misconceptions related with the biochemistry of Tau. The commercially available immunotherapies were also investigated. Thioflavin T fluorescence and Congo-Red UV-Vis spectroscopy were utilized to monitor Tau441 aggregation and aggregate dissolution in the presence of various antibodies. The effects of monoclonal, polyclonal, and commercial antibodies on Tau biochemistry will be described towards an alternative therapeutic treatment for neurodegenerative diseases.References[1] Alonso, A. C., Grundke-Iqbal, I. and Iqbal, K. (1996). Alzheimer's disease hyperphosphorylated Tau sequesters normal Tau into tangles of filaments and disassembles microtubules. Nature Med. 2, 783-787.[2] Mandelkow, E. M. and Mandelkow, E. (2012). Biochemistry and cell biology of Tau protein in neurofibrillary degeneration. Cold Spring Harb Perspect Med;2:a006247.

Spectroscopic investigations:  The effects of antibodies on Tau protein biochemistry

248th National Meeting (2014)

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