ABSTRACT

The 1980s experienced a revolution in molecular genetics due to the development of techniques such as the polymerase chain reaction (PCR) and advances in automated instrumentation that have facilitated large-scale sequencing. The federally funded Human Genome Project and the first generation genomics companies have successfully capitalized on these technological advances to identify novel genes and map a large portion of the normal human genome in a relatively short period of time. By contrast, the determination of the function of the novel genes, as well as the identification of genes involved in specific human diseases, have lagged far behind. The recent development, in the early 1990s, of molecular biological techniques such as subtractive hybridization, degenerate PCR, and differential display, in conjunction with advances in cellular and animal models of human diseases, positions us for a targeted approach to rapidly identify and determine the function of novel genes that contribute to particular disease processes. This chapter will provide a brief background on the inflammatory aspects of neurodegenerative diseases, and an overview of the rationale and strategies for the identification of novel genes in brain that may contribute to common pathways involved in neuronal degeneration and regeneration. While the technological approaches outlined in the chapter are described in the context of their utility for the study of neurodegenerative diseases, they can also be applied to a wide range of non-neurological human diseases.