Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insights into factors underlying causes of familial Alzheimer's disease (AD), such as mutant forms of beta-amyloid precursor protein and presenilins, and those conferring increased risk of sporadic AD, such as isoforms of apolipoprotein E and polymorphisms of alpha2-macroglobulin, have been rapidly emerging. However, mechanisms through which amyloid beta-peptide (Abeta), the fibrillogenic peptide most closely associated with neurotoxicity in AD, exerts its effects on cellular targets have only been more generally outlined. Late in the course of AD, when Abeta fibrils are abundant, non-specific interactions of amyloid with cellular elements are likely to induce broad cytotoxicity. However, early in AD, when concentrations of Abeta are much lower and extracellular deposits are infrequent, mechanisms underlying cellular dysfunction have not been clearly defined. The key issue in elucidating the means through which Abeta perturbs cellular properties early in AD is the possibility that protective therapy at such times may prevent cytotoxicity at a point when damage is still reversible. This brief review focusses on two cellular cofactors for Abeta-induced cellular perturbation: the cell surface immunoglobulin superfamily molecule RAGE (receptor for advanced glycation endproducts) and ABAD (Abeta binding alcohol dehydrogenase). Although final proof for the involvement of these cofactors in cellular dysfunction in AD must await the results of further in vivo experiments, their increased expression in AD brain, as well as other evidence described below, suggests the possibility of specific pathways for Abeta-induced cellular perturbation which could provide future therapeutic targets.
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PMID:Cellular cofactors potentiating induction of stress and cytotoxicity by amyloid beta-peptide. 1089 40

Despite remarkable progress in diagnosis and understanding of risk factors, cardiovascular disease (CVD) remains still the leading cause of morbidity and mortality in the world's developed countries. The metabolic syndrome, a cluster of risk factors (visceral obesity, insulin resistance, dyslipidaemia, and hypertension), is increasingly being recognized as a new risk factor for type 2 diabetes and atherosclerotic cardiovascular disease. Nevertheless, there is wide variation in both the occurrence of disease and age of onset, even in individuals who display very similar risk profiles. There is now compelling evidence that a complex interplay between genetic determinants and environmental factors (still largely unknown) is the reason for this large inter-individual variation in disease susceptibility. The purpose of the present review is to describe the current status of our knowledge concerning the gene-environment interactions potentially implicated in the pathogenesis of metabolic syndrome, diabetes and cardiovascular disease. It focuses predominantly on studies of genes (peroxisome proliferator-activated receptor-gamma, alcohol dehydrogenase type 1C, apolipoprotein E, glutathione S-transferases T1 and M1) that are known to be modified by dietary and lifestyle habits (fat diet, intake of alcohol and smoking habit). It also describes the limited current understanding of the role of genetic variants of xenobiotic metabolizing enzymes and their interactions with environmental toxicants. Additional studies are needed in order to clarify whether inter-individual differences in detoxification of environmental toxicants may have an essential role in the development of CVD and contribute to the emerging field of "environmental cardiology". Such knowledge may be particularly relevant for improving cardiovascular risk stratification and conceiving the development of "personalized intervention program".
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PMID:Metabolic syndrome, diabetes and atherosclerosis: influence of gene-environment interaction. 1902 10

Human settlement from the African ancestral home was accompanied by cultural and genetic adaptation to new habitat conditions (climate, infections, diet, etc.). We previously suggested for the first time an approach to the identification of human genes presumably involved in adaptation to evolutionary new environmental factors based on a combination of genetic and humanitarian methods of study. In order to search for the genes involved in adaptation and for environmental factors (to which this adaptation occurs), we attempted to find correlations between the population allele frequencies of the studied gene and formalized descriptions of peculiarities of the habitat of ethnic groups given in "Ethnographic Atlas" by G. P. Murdock. In the presented review, we summarized our own data on an experimental determination of the allele frequencies for lactase (LCT*), apolipoprotein E (APOE), and alcohol dehydrogenase (ADH1B) genes in populations of Russia. Based on these data and available materials of other investigators, we developed maps of worldwide allele frequency distribution for these genes. We detected a correlation of allele frequencies of these genes in populations with the presence of certain factors of the environment that these populations inhabit. It was also confirmed that the evolutionarily young LCT*-13910T allele, which determines lactase persistence and the possibility of milk consumption in adults, is distributed in populations for which dairy animal husbandry is typical. During the analysis of 68 populations, we for the first time demonstrated that the frequency of the APOE e4 allele (which is ancestral for humans and influences the lipid metabolism) is higher in groups with a high contribution of hunting and gathering. Our data are in favor of the hypothesis that it was exactly the e4 allele that was a subject for selection, while the e3 allele was less important for adaptation. We also for the first time demonstrated that the evolutionarily young ADH1B*48His allele (which determines a high rate of ethanol metabolism into acetaldehyde) is presented with a large frequency in those populations where filariasis is endemic. The obtained data indicate the possible involvement of endogenous ADH1B gene substrates or their metabolites in the resistance to filaria and open a new path to the development of drugs for this widespread human disease.
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PMID:[Combination of Genetic and Humanitarian (Cross-Cultural) Methods for the Identification of Human Genes Involved in the Process of Adaptation to Evolutionary New Environmental Factors]. 2608 23