Abnormal and excessive tau phosphorylation commonly characterizes Alzheimer’s disease (AD) neuropathology through neurofibrillary tangles (NFTs) causing axonal dysfunction and microtubular instability. Essential to DNA repair, protein modification, and gene expression, the methionine cycle generates a methyl group upon the conversion of S-adenosyl-methionine to S-adenosyl-homocysteine, which can activate protein phosphatase 2A (PP2A) and leucine carboxyl methyltransferase 1 interactions in neurons.1,2 These interactions are known to target serine/threonine phosphate groups prevalent in hyperphosphorylated tau, and prior studies have demonstrated increased aggregate formation in vivo upon PP2A inhibition.1,2 Furthermore, increased levels of homocysteine, a byproduct of the methionine cycle normally converted back into methionine or anti-oxidative glutathione, is strongly linked to the progression of AD.3 This suggests insufficient methionine resynthesis allowing the hyperphosphorylation of tau to form NFTs. Biochemical analysis of the different pathways homocysteine metabolism undertakes show many similarities to digestive reactions in the liver of the reactive intermediate imine deaminase A homolog (UK114) enzyme. We are studying the potential interactions and role of UK114 in transfected Chinese Hamster Ovary cells by recording protein expression levels via Western blot. The transfected cells are subjected to various conditions either translatable with symptoms of AD or saturated with components of the methionine cycle that are potentially catalyzed by UK114. The results of these studies will further expand our understanding of the methionine cycle in relation to AD pathology, as well as explore the antioxidant uses of UK114 in an immunological scope.
*LOUD THUD as Dang accidentally knocks over a giant bottle*
“Is Dang throwing things again? Bad boy.”-Joan
“Let’s go stuff some squirrels and hamsters in a fridge to induce torpor!”-Dr. Colton
“We already tried that. It didn’t work.”-Joan
“PARTY POOPER!”-Dr. Colton
“Wow, big pellets! This sample is good!
*BCA subsequently fails. negative protein concentrations returned. half the trial ruined*
“What’s wrong with your milk? :/”-Huifang as she throws away milk and goes to her own stash
“And one day, you’ll be like these two amazing children. One graduating with distinction and the other just a lowly freshman!”-Dr. Colton
1.Qian, W., Shi, J., Yin, X., Iqbal, K., Grundke-Iqbal, I., Gong, C., Liu, F. (2010). PP2A Regulates Tau Phosphorylation Directly and also Indirectly via Activating GSK-3β. Journal of Alzheimer’s Disease, 19(4), 1221-1229.https://content.iospress.com/articles/journal-of-alzheimers-disease/jad01317
2.Stanevich, V., Jiang, L., Satyshur, K. A., Li, Y., Jeffrey, P. D., Li, Z., … Xing, Y. (2011). The structural basis for tight control of PP2A methylation and function by LCMT-1. Molecular Cell, 41(3), 331–342. http://doi.org/10.1016/j.molcel.2010.12.030
3.Seshadri, S., Beiser, A., Selhub, J., Jacques, P. F., Rosenberg, I. H., D’Agostino, R. B., Wilson, P. W.F., Wolf, P. A. (2002). Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer’s Disease. The New England Journal of Medicine, 346, 476-483.