This review on selected neurodegenerative diseases, including Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and Parkinson's disease, and frontotemporal dementia with Parkinsonism (FTD-P), focuses on the ways by which genetically engineered models have clarified the mechanisms of these disorders and have identified new targets for therapy, and been used to test new treatment strategies. These neurodegenerative diseases are some of the most challenging diseases in medicine because of their general prevalence, cost, lack of mechanism-based treatments, and impact on individuals and caregivers (Lipp & Wolfer, 1998; Wong et al., 2002). The classical clinical phenotypes are, for the most part, quite distinct and reflect the dysfunction and death of specific populations of neurons. These brain lesions are characterized by the presence of intracellular or extracellular peptides/aggregates, which appear to be critical contributors to neurotoxicity, partially damaging to synapses. Genetic risk factors influence these age-associated, chronic illnesses. In rare instances, cases are inherited in Mendelian fashion (usually as autosomal dominants). Susceptibility genes, environmental risk factors, or other influences remain to be defined. Information from genetics has allowed investigators to express or to target genes in efforts to model these diseases and to study the (Armstrong et al., 1996) molecular participants critical in pathogenic pathways. This body of research is the principal topic of this review.
In this review, we emphasize the value of genetically engineered mouse models for studies of mechanisms and for experimental therapeutics, but we also briefly describe the extraordinary utility of non-mammalian genetic models.