RESUMO
INTRODUCTION: Today, scientists accept that the central nervous system of an adult possesses considerable morphological and functional flexibility, allowing it to perform structural remodelling processes even after the individual is fully developed and mature. In addition to the vast number of genes participating in the development of memory, different known epigenetic mechanisms are involved in normal and pathological modifications to neurons and therefore also affect the mechanisms of memory development. DEVELOPMENT: This study entailed a systematic review of biomedical article databases in search of genetic and epigenetic factors that participate in synaptic function and memory. CONCLUSIONS: The activation of gene expression in response to external stimuli also occurs in differentiated nerve cells. Neural activity induces specific forms of synaptic plasticity that permit the creation and storage of long-term memory. Epigenetic mechanisms play a key role in synaptic modification processes and in the creation and development of memory. Changes in these mechanisms result in the cognitive and memory impairment seen in neurodegenerative diseases (Alzheimer disease, Huntington disease) and in neurodevelopmental disorders (Rett syndrome, fragile X, and schizophrenia). Nevertheless, results obtained from different models are promising and point to potential treatments for some of these diseases.
Assuntos
Epigênese Genética , Memória/fisiologia , Doenças Neurodegenerativas/genética , Transtornos do Neurodesenvolvimento/genética , Humanos , Transtornos da Memória/genética , Plasticidade Neuronal/genética , NeurôniosRESUMO
INTRODUCTION: Today we know of a group of mutations caused by the expansion of nucleotide triplets, which are very unstable in meiosis and mitosis. Four types of triplets have the capacity for pathogenic expansion in human beings (CGG/ GCC, CAG/GTC, CTG/GAC and GAA/CTT) and maybe located both in coding sequences (bulbospinal muscular atrophy, Huntington's disease and certain spinocerebellar ataxias) and non-coding sequences (fragile X syndrome, Friedreich's ataxia, myotonic dystrophy). Trinucleotide expansion may lead to gains or losses in gene functioning and seems to be associated to a variety of factors, some of which are directly related with the expansive process (cis-acting) and others whose interaction with the triplets helps to make them increasingly more unstable (trans-acting). Medium-sized expansions (pre-mutations), although clinically silent, do show a marked tendency to expand into complete mutations during the transition along the germinal line. The models that have been proposed to explain triplet expansion involve gene recombination and replication processes; however, they have not fully succeeded in explaining the phenomena related to mutation or phenotypic expression in these diseases. DEVELOPMENT: This work examines the most recent concepts related to the dynamic mutation processes that give rise to human diseases; it also reviews the most important clinico-biological aspects observed in those diseases. CONCLUSIONS: Dynamic mutation processes represent a new concept in the molecular biology of gene mutations. An ever increasing number of pathologies are caused by this type of DNA alterations, which, as a whole, display very interesting clinico-biological characteristics.