Published online by Cambridge University Press: 12 October 2009
The neurodegenerative diseases are an extraordinary challenge for science and medicine due to the grave nature of these illnesses, their prevalence, and their impact on individuals and caregivers. The most prevalent of these age-associated, chronic, illnesses include Alzheimer's disease (AD) and Parkinson's disease (PD); other examples include the prion disorders, amyotrophic lateral sclerosis, and the trinucleotide (CAG) repeat diseases. All of these diseases are characterized by well-defined clinical syndromes with progressive courses; evidence of dysfunction/death of specific populations of neurons; specific pathological and biochemical abnormalities; and the presence of intra- or extracellular protein aggregates (for review see Price et al., 1998). At present, there are treatments available that will ameliorate some of the symptoms, but none of these significantly alter the course of disease.
With the exception of the CAG repeat disorders, most cases of neurodegenerative disease arise from unknown aetiologies. However, a very small subset of cases are inherited, usually in an autosomal dominant fashion, and the identification of mutations in specific genes for some of these disorders has provided new opportunities to investigate the molecular participants in disease processes and to explore pathogenic mechanisms in model systems. Perhaps the greatest use of genetically engineered models has been to allow investigators to assess the in vitro and in vivo consequences of mutations in, or deletions of, genes implicated in neurodegenerative disorders. Knocking-out or over-expressing the products of genes that influence the pathways leading to disease has proved to be an extremely valuable strategy for examining some of the mechanisms and potential therapeutic targeting.