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Invertebrate models of lysosomal storage disease: what have we learned so far?

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Invertebrate Neuroscience

Abstract

The lysosomal storage diseases (LSDs) collectively account for death in 1 in 8,000 children. Although some forms are treatable, they are essentially incurable and usually are lethal in the first decade of life. The most intractable forms of LSD are those with neuronal involvement. In an effort to identify the pathological signaling driving pathology in the LSDs, invertebrate models have been developed. In this review, we outline our current understanding of LSDs and recent findings using invertebrate models. We outline strategies and pitfalls for the development of such models. Available models of LSD in Drosophila and Caenorhabditis elegans are uncovering roles for LSD-related proteins with previously unknown function using both gain-of-function and loss-of-function strategies. These models of LSD in Drosophila and C. elegans have identified potential pathogenic signaling cascades that are proving critical to our understanding of these lethal diseases.

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Abbreviations

LSD:

Lysosomal storage disease

BBB:

Blood/brain barrier

ERT:

Enzyme replacement therapy

MPS:

Mucopolysaccharidosis

MLS:

Mucolipidosis

GAGs:

Glycosaminoglycans

NCL:

Neuronal ceroid lipofuscinosis

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Acknowledgments

We thank Sangeeta Chawla for comments on the manuscript. We thank the BBSRC (for a Quota studentship to S. Hindle, grant BB/I012273/1 to STS) and MRC (grant G0400580 to STS,) for funding. Sarita Hebbar is supported by a Wellcome Trust-DBT India Alliance Senior Fellowship awarded to Dominik Schwudke, NCBS, India.

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  1. Samantha Hindle

    Present address: Department of Anesthesia, University of California San Francisco, Genentech Hall, 600 16th Street, San Francisco, CA, USA

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  1. Department of Biology (Area 9), University of York, Wentworth Way, Heslington, York, YO10 5DD, UK

    Samantha Hindle & Sean T. Sweeney

  2. Hull-York Medical School, University of York, York, YO10 5DD, UK

    Samantha Hindle & Sean T. Sweeney

  3. National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bellary Road, Bangalore, 560065, India

    Sarita Hebbar

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Hindle, S., Hebbar, S. & Sweeney, S.T. Invertebrate models of lysosomal storage disease: what have we learned so far?. Invert Neurosci 11, 59–71 (2011). https://doi.org/10.1007/s10158-011-0125-2

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