CBR member Sanela Martic publishes research related to Alzheimer's disease

CBR member Sanela Martic publishes research related to Alzheimer's disease

Assistant Professor Sanela Martic, of the Department of Chemistry, is the most recent member to join the Center for Biomedical Research. Martic’s laboratory is focused on the misfolding of peptides and proteins that are linked to degeneration. The aim of her current research is to understand the biochemistry of tau protein aggregation and phosphorylation, and to determine their influence on microtubule stability. The tau protein may play a key role in the development of Alzheimer’s disease.

Martic and her graduate student Jose Esteves-Villanueva recently published an article about the electrochemical detection of anti-tau antibodies binding to tau protein in the March 1, 2016 issue of the journal Analytical Biochemistry (Volume 496, Pages, 55-62). Esteves-Villanueva, the lead author on the study, graduated in July 2015 with his masters degree in Chemistry.

Below is an excerpt from the introduction of their article (with references removed).

“Tau protein has a structural role in neurons, where it stabilizes microtubules, further maintaining cell integrity. Normal tau is partially phosphorylated by protein kinases, but malfunctioning tau is hyperphosphorylated, which promotes detachment from microtubules and cell death. Glycogen synthase kinase (GSK)-3beta protein kinase is the most biologically relevant enzyme in tau phosphorylations due to its aberrant phosphorylation at multiple Ser and Thr residues. GSK-3beta phosphorylation of tau has been well characterized by Western blotting and mass spectrometry. The tau pathology has been linked to neurodegenerative diseases, including dementia and Alzheimer's disease. Currently, no cure exists for neurodegenerative diseases, but multiple avenues have been explored toward therapeutics for tauopathies. Inhibiting tau phosphorylation is one of the therapeutic avenues toward prevention of the onset of tau pathology. Immunotherapies have recently gained tremendous interest due to evidence that extracellular tau causes cell-to-cell toxicity. In transgenic tauopathy mice that express human tau gene mutations, immunotherapies have been implemented….

Here we report on the electrochemical detection of GSK-3beta-catalyzed phosphorylation of Tau441 and effects of anti-tau antibodies on phosphorylation. EIS [Electrochemical impedance spectroscopy] was used to determine charge transfer resistance (Rct) change induced by phosphorylation and to determine the inhibitory effects by anti-tau antibodies to nonphosphorylated tau-Au film. In addition, the antigen-antibody binding was also evaluated.”