Acetaldehyde-protein adducts have been detected within the white matter, frontal cortex, midbrain, dentate gyrus, and cerebellum in ethanol-fed rats, and in the frontal LEE011 supply cortex and midbrain of an alcoholic. Furthermore, alcohol metabolism may also trigger the production of detrimental protein adducts from products of lipid peroxidation, including 4-hydroxy-2-nonenal, that can bind tubulins and trigger loss of microtubular structures via an increase in their insolubility. In liver, ethanol consumption also increases protein damage as isoaspartate via the impact of ethanol on the methionine metabolic pathway. Ethanol consumption triggers a reduction in the levels of the methyl donor S-adenosylmethionine, and an increase in the levels of the metabolite S-adenosylhomocysteine. This reduced SAM:SAH ratio inhibits the activity of many methyltransferases including protein isoaspartyl methyltransferase, an enzyme that functions to trigger the repair of isoaspartate damaged proteins. However, it has yet to be determined whether a similar mechanism of ethanol-induced inhibition of PIMT and elevation of isoaspartate damage exists in brain tissue. Regional brain alcohol-induced pathology may impact upon motor-neuron function, and also influence cognitive behaviour. In an attempt to assess protein damage within a brain region involved in cognitive and social behaviour, we first examined postmortem brain tissue from the prefrontal cortex from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. We compared control and alcoholic neuronal tissue histology, and then employed protein profiling to identify prominent neuronal tissue protein changes. An identification of the major brain protein changes provided an insight into structural damage in alcoholic’s brains, for which functional deficits were extrapolated. An examination of the molecular abnormalities that arise as a consequence of cumulative ethanol intoxications will assist with an understanding of the development of tissue pathology. In addition, a characterisation of ethanol-induced molecular changes may also provide an insight into the molecular adaptations associated with tolerance, dependence, and an alcoholic’s behavioural abnormalities. Collectively, WY 14643 PPAR inhibitor research in this field will provide a basis for targeted therapeutics that counter debilitating morbidity, and lower the incidence 
of mortality. We assessed alcohol-related neuronal tissue damage of the prefrontal cortex using light microscopy, and were intrigued to see clear histological distinction between cells of alcoholics and their matched controls. This led us to undertake one dimensional protein profiling of cytosolic proteins from alcoholics and controls and we identified the major protein losses as that from a- and btubulins, and spectrin b-chain. Alpha and b-tubulins localise as heterodimers, and are major components of microtubules. Microtubules are non-covalent cytoskeletal polymers that provide a cellular protein network. Microtubules influence cell shape, motility, and stability, and are central to the functioning of countless cellular processes including mitosis, and vesicular transport. Microtubules exist as both dynamic and stable polymers, with transitions between these states in sub-populations of microtubules influenced by PTMs and microtubule-associated proteins.