Human Genetics

Biography

Biography: Oscar Teijido

Abstract

Cerebrovascular and neurodegenerative disorders are among the leading causes of death in the World, according to the WHO. A number of these disorders are characterized by the onset of dementia. Alzheimer’s disease (AD) is the major cause of dementia in Western countries, affecting 45-60% of the population, followed by vascular dementia (VD) and mixed dementia (MD), with prevalences of 30-40% and 10-20%, respectively. Epigenomic mechanisms (DNA methylation, chromatin remodeling/histone modifications, miRNA regulation) are involved in the transcriptional and post-translational regulation of genes in physiological and pathological conditions leading to potentially reversible phenotypes. Epigenetics is sited among the major regulatory elements that control metabolic pathways at the molecular level, which allows a deeper study of complex multifactorial diseases, such as dementia-related disorders. Therefore, epigenomic signatures may help in the prediction, early diagnosis, and prognosis of those pathologies. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to epigenetically regulated genes. We have evaluated the main epigenetic mechanisms affecting genes associated with dementia-related disorders, such as Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). We also evaluated genes related with lipid metabolism and vascular physiology which are not directly involved in brain disorders, although their epigenetic profile may be nevertheless associated with dementia-related disorders. Epigenetic drug discovery, application of pharmacoepigenomic procedures for personalized therapeutics, novel approaches to decode and resolve drug resistance, and targeting miRNAs in prevention and treatment of dementia-related disorders are promising areas of future development.