Nucleic Acid Aptamer Selection against Tau Microtubule-Associated Protein
Tau proteins are expressed by functional neurons and oligodendrocytes to stabilize microtubules. They generally consist of two main binding domains: a projection domain that interacts with neural plasma membrane and cytoskeletal elements, and the microtubules binding domain, which is responsible for microtubule polymerization and stabilization. Six main isoforms of tau exist, differing in their number of binding sites due to alternative splicing of exons.
Hyperphosphorylation of the tau protein leads to the self-assembly of neurofibrillary tangles as excessive binding pairs helical and straight filaments together. Neurofibrillary tangles are responsible for a specific class of neurodegenerative diseases that includes Alzheimer's and Parkinson's disease: tauopathy. Aggregation of hyperphosphorylated tau protein accumulates in the brain, leading to apoptosis of neurons.
One approach to inhibiting this process incorporates nucleic acid ligands called aptamers. Aptamers bind with high specificity and high affinity to proposed protein targets for diagnostic and therapeutic purposes. An aptamer against Tau protein could potentially either prevent the formation of neurofibrillary tangles prominent in neurodegenerate diseases or as a diagnostic tool allowing for the early detection of mutated tau protein. Figure 1 depicts tangled clumps of Tau proteins, leading to disintegrating microtubules.
Figure 1: As clumps of Tau proteins tangle together, microtubule subunits deteriorate.
Tau protein can be ordered online through the company rPeptide. The catalog number for my proposed target is T-1005-1. This specific isomer of the protein contains only the binding domain responsible for supporting microtubules. Choosing the protein with the least binding sites allows for greater specificity when selecting for an aptamer. Ordering a 100ug aliquot of the target protein costs approximately $375 and can be ordered by reaching this number: (678) 753-0747.
Huang, Austin. "The Effect of a ΔK280 Mutation on the Unfolded State of a
Microtubule-Binding Repeat in Tau." Computational Biology. Public Library
of Science, 22 Aug. 2008. Web.
"rPeptide Data Sheet." rPeptide. Web.
"Tau Protein in Alzheimers Disease." Edinformatics -- Education for the Information Age. 2009. Web.
This is the link for my Research Proposal.
This is the link for my first Progress Report.
Here is my final research paper, outlining the progress on my selection for this semester.