Genomics, a discipline dedicated to the analysis and sequencing of genomes, has the potential to revolutionize neuroscience and the discovery of drugs for neurological diseases. The mapping of the human genome, together with advances in functional genomics and bioinformatics, has inaugurated a new era in research on the nervous system, allowing the identification of numerous human genes in silico and their possible relationship with complex neurological diseases. (WAHLESTEDT, 2001)
Prioritizing and validating these genes as drug targets is a crucial challenge. Currently, most drugs target four main classes of gene products: 7-TM receptors, ion channels, nuclear hormone receptors, and enzymes. However, the discovery of new genes and the complexity of the nervous system require innovative approaches to identify and validate promising targets. (WAHLESTEDT, 2001)
DNA microanalyses, although useful, have limitations in terms of sensitivity and specificity, especially in neuroscience, where small changes in gene expression can have a large functional impact. Techniques such as quantitative PCR and radioactivity-based methods demonstrate greater sensitivity in detecting changes in gene expression in the human brain. (WAHLESTEDT, 2001)
In vivo validation of drug targets in the nervous system usually involves the manipulation of gene expression in animal models. The gene knockdown or knockout technique, using antisense oligonucleotides, has been shown to be effective, especially in the central nervous system, due to the low nuclease activity in the cerebrospinal fluid. (WAHLESTEDT, 2001)
Although animal models such as knockout mice are widely used, their limitations, such as the influence of development on phenotypes and the presence of compensatory mechanisms, require caution in the interpretation of results. Conditional knockout strategies, which allow gene deletion with temporal and spatial control, offer a promising alternative, despite the technical challenges and high costs. (WAHLESTEDT, 2001)
RNA interference (RNAi) in non-mammalian organisms, such as C. elegans, is emerging as an effective and easy-to-apply knockdown technique. RNAi, which is based on the ability of double-stranded RNA (dsRNA) to degrade the corresponding mRNA, simplifies the manipulation of gene expression and functional analysis in in vivo studies. (WAHLESTEDT, 2001)
Understanding of the genetic basis of human neurological and behavioral diseases is still limited, especially in complex disorders such as schizophrenia. The genetics of complex diseases is challenging, and replication of results across different laboratories and cohorts is essential to confirm the association of genes with increased risk of disease. (WAHLESTEDT, 2001)
Single nucleotide polymorphisms (SNPs), which account for the majority of human genetic variability, are the subject of intense research. The identification and analysis of SNPs, especially those affecting genome coding (cSNPs) and protein function, are crucial for understanding disease predisposition and developing targeted therapies. (WAHLESTEDT, 2001)
In short, genomics and related technologies are driving significant advances in neuroscience and drug discovery. The growing understanding of the human genome and the application of innovative gene manipulation approaches promise to unravel the molecular mechanisms of neurological diseases and pave the way for new effective therapies. (WAHLESTEDT, 2001)
Reference
WAHLESTEDT, C. Using genomics to understand the nervous system. Drug Discovery Today: Genomics Supplement, vol. 6, no. 15, p. S81-S85, 2001.
