Transgenic mouse models of neurodegenerative disease: opportunities for therapeutic development.
Neurodegenerative diseases present an extraordinary challenge for medicine due to the grave nature of these illnesses, their prevalence, and their impact on individuals and caregivers. The most common of these age-associated chronic illnesses are Alzheimer's disease (AD) and Parkinson's disease (PD); other examples include the prion disorders, amyotrophic lateral sclerosis (ALS), and the trinucleotide (CAG) repeat diseases. All of these diseases are characterized by well-defined clinical syndromes with progressive courses that reflect the dysfunction and eventual loss of specific neuronal populations. Current therapies provide only symptomatic relief; none significantly alter the course of disease. We describe here how transgenic mice designed to model these diseases have substantially contributed to the identification and validation of many promising new therapies, and conversely how they have quickly and cost effectively eliminated several targets with unrealized expectations.
Jankowsky
Joanna L
JL
Department of Pathology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Building Room 558, Baltimore, MD 21205, USA.
Savonenko
Alena
A
Schilling
Gabriele
G
Wang
Jiou
J
Xu
Guilian
G
Borchelt
David R
DR
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D000818:Animals; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000235:genetics / Q000628:therapy; D051379:Mice; D008822:Mice, Transgenic; D016472:Motor Neuron Disease / Q000235:genetics / Q000473:pathology / Q000628:therapy; D009154:Mutation; D009420:Nervous System / Q000378:metabolism / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D013132:Spinocerebellar Degenerations / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D018911:Trinucleotide Repeats / Q000235:genetics
D016229:Amyloid beta-Peptides