Probing Mechanisms That Underlie Human Neurodegenerative Diseases in Drosophila

The fruit fly, Drosophila melanogaster , is an excellent organism for the study of the genetic and molecular basis of metazoan development. Drosophila provides numerous tools and reagents to unravel the molecular and cellular functions of genes that cause human disease, and the past decade has witne...

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Bibliographic Details
Published in:Annual review of genetics 2012-01, Vol.46 (1), p.371-396
Main Authors: Jaiswal, M, Sandoval, H, Zhang, K, Bayat, V, Bellen, H.J
Format: Article
Language:English
Subjects:
Alzheimer's disease
amyotrophic lateral sclerosis
Animals
Autophagy
Biodegradation
Disease Models, Animal
Drosophila melanogaster
Drosophila melanogaster - genetics
Drosophila melanogaster - metabolism
Gene loci
Genetics
Humans
Insects
Longevity - genetics
Metazoa
Mitochondria - metabolism
Mitochondria - pathology
Neurodegeneration
Neurodegenerative Diseases - genetics
Neurodegenerative Diseases - metabolism
Neurodegenerative Diseases - pathology
Neurons - metabolism
Neurons - pathology
Neurotoxicity
Oxidative Stress
Parkinson's disease
Proteasome Endopeptidase Complex - genetics
Proteasome Endopeptidase Complex - metabolism
protein degradation
Quality control
Reactive Oxygen Species - metabolism
Reagents
Synaptic Transmission
Ubiquitin - genetics
Ubiquitin - metabolism
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Summary:The fruit fly, Drosophila melanogaster , is an excellent organism for the study of the genetic and molecular basis of metazoan development. Drosophila provides numerous tools and reagents to unravel the molecular and cellular functions of genes that cause human disease, and the past decade has witnessed a significant expansion of the study of neurodegenerative disease mechanisms in flies. Here we review the interplay between oxidative stress and neuronal toxicity. We cover some of the studies that show how proteasome degradation of protein aggregates, autophagy, mitophagy, and lysosomal function affect the quality control mechanisms required for neuronal survival. We discuss how forward genetic screens in flies have led to the isolation of a few loci that cause neurodegeneration, paving the way for large-scale systematic screens to identify such loci in flies as well as promoting gene discovery in humans.
ISSN:0066-4197
1545-2948
DOI:10.1146/annurev-genet-110711-155456