Abdulbaki Agbas

Research Assistant Professor

Education Background

• B.S. Chemistry, 1980 - Ataturk University, Erzurum/Turkey
• M.Sc. Biochemistry, 1985 - Ataturk University, Erzurum/Turkey
• Ph.D. Biochemistry, 1988 - Joszef Attila Science Univ., Szeged/Hungary
• University Docent (Associate Professor), Biochemistry, 1998 - The Higher Education Council, Turkey

Research Interests

• The oxidative modifications of NMDA receptor complex, Ca2+ dysregulation in cells, and the process of aging in the brain. The free radical theory of aging proposes that the slow generation of reactive oxygen species (ROS) results in cumulative damage to critical cellular components, and eventually leads to age-related pathological conditions. In normal and premature aging processes, as well as in certain degenerative diseases, oxidatively modified proteins, DNA, and lipids are oxidized by ROS and their accumulation is a possible contribution to the cell aging. I explore is whether under the conditions of metabolic or oxidative stress, the activity of NMDA receptors may be mediated. In vitro studies have shown that NMDA receptor functions by a mechanism involving oxidation of sulfhydryl residues, i.e., cysteines, in a key subunit of the receptor, the NR1. I am studying whether ROS during oxidative stress in brain in vivo control the over activation of NMDA receptor complex.
• To study the oxidation of protein phosphatases (Protein phosphatases 1 and 2B) in senescent animals. Since long-term depression (LTD) is enhanced in neurons of senescent animals and this enhancement is linked to memory deficiency, protein phosphatase 2B (Calcineurin) may have contribute to LTD enhancement, therefore, to memory formation in senescent animals. How the oxidation of Calcineurin mediates its activity is under investigation.
• To address the question of possible selective trafficking to dendrites of mRNAs that represent certain exonic splice variants of NR1. New protein synthesis is a necessary biochemical process in the establishment of the long-lasting phase of LTP. Although the precise mechanisms for the regulation of new protein synthesis during the establishment of the long-lasting phase of LTP have not yet been fully defined, one mechanism suggested is that of localized protein synthesis in dendritic shafts or post-synaptic spines.
• This is newly renewed 3rd 5-year NIAA program project. An important aspect of brain aging is the increased glutamate (Glu) release and accumulation in the extracellular space of neurons. Age-associated increases in extracellular Glu occur because of partial loss of activity of Glu transporters. Essentially all neurons in the central nervous system (CNS) are exposed to elevated extracellular Glu, yet not all brain regions suffer equally. The sensitivity of certain neurons to the toxic effects of Glu produced through Ca2+- and oxidative stress-mediated processes, increases with age. At present time, we don't know the underlying reasons that why certain neurons are vulnerable to Glu toxicity. Also, no animal model of age-associated increases in Glu release in CNS is available to determine how excess Glu produces its effect on aging neurons. We have generated transgenic (Tg) mice that have extra copies of the gene for Glu dehydrogenase 1 (GLUD1), a mitochondrial enzyme considered to be a rate-limiting, step in the biosynthesis of Glu as a transmitter. The GLUD1 transgene, introduced under the control of a neuron-specific promoter, is expressed only in neurons. GLUD1 mice have higher levels of depolarization-induced Glu release than wild type (wt) and suffer losses in specific neuronal populations. GLUD1 mice also have a shortened life span without exhibiting severe neurological dysfunction. We are testing the hypothesis that excess extracellular Glu in aging brain initiates events that lead to altered metabolic states in CNS, damage to select populations of neurons, an imbalance between damage and recovery, metabolic stress in peripheral tissues, and decreased longevity.

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