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15 - Selected genetically engineered models relevant to human neurodegenerative disease

from Part I - Basic aspects of neurodegeneration

Published online by Cambridge University Press:  04 August 2010

M. Flint Beal ,
Anthony E. Lang  and
Albert C. Ludolph
By
Donald L. Price ,
David R. Borchelt ,
Michael K. Lee  and
Philip C. Wong
M. Flint Beal
Affiliation:
Cornell University, New York
Anthony E. Lang
Affiliation:
University of Toronto
Albert C. Ludolph
Affiliation:
Universität Ulm, Germany
Donald L. Price
Affiliation:
Department of Pathology, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
David R. Borchelt
Affiliation:
Department of Neurology, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Michael K. Lee
Affiliation:
Department of Neurscience, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Philip C. Wong
Affiliation:
Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Summary

Introduction

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.

Type
Chapter
Information
Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
 , pp. 176 - 195
Publisher: Cambridge University Press
Print publication year: 2005

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