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Axonal transport defects: a common theme in neurodegenerative diseases

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Abstract

A core pathology central to most neurodegenerative diseases is the misfolding, fibrillization and aggregation of disease proteins to form the hallmark lesions of specific disorders. The mechanisms underlying these brain-specific neurodegenerative amyloidoses are the focus of intense investigation and defective axonal transport has been hypothesized to play a mechanistic role in several neurodegenerative disorders; however, this hypothesis has not been extensively examined. Discoveries of mutations in human genes encoding motor proteins responsible for axonal transport do provide direct evidence for the involvement of axonal transport in neurodegenerative diseases, and this evidence is supported by studies of animal models of neurodegeneration. In this review, we summarize recent findings related to axonal transport and neurodegeneration. Focusing on specific neurodegenerative diseases from a neuropathologic perspective, we highlight discoveries of human motor protein mutations in some of these diseases, as well as illustrate new insights from animal models of neurodegenerative disorders. We also review the current understanding of the biology of axonal transport including major recent findings related to slow axonal transport.

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Acknowledgements

We are indebted to the patients and their caregivers who have facilitated research on these neurodegenerative diseases. V.M.Y.L. is the John H. Ware, 3rd Professor of Alzheimer’s disease research. J.Q.T. is the William Maul Measey-Truman G. Schnabel, Jr. Professor of Geriatric Medicine and Gerontology. The authors acknowledge support for their research from the NIH [P01 AG09215, P30 AG10124, P01 AG11542, P01 AG14382, P01 AG14449, P01 AG17586, P01 NS044233]. Due to space limitations, many references to primary literature cannot be included but they may be found in reviews cited here.

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  1. Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, and Institute on Aging, University of Pennsylvania School of Medicine, HUP, Maloney Building 3rd Floor, 3600 Spruce Street, Philadelphia, PA, 19104-4283, USA

    Subhojit Roy, Bin Zhang, Virginia M.-Y. Lee & John Q. Trojanowski

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  1. Subhojit Roy
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Correspondence to John Q. Trojanowski.

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Roy, S., Zhang, B., Lee, V.MY. et al. Axonal transport defects: a common theme in neurodegenerative diseases. Acta Neuropathol 109, 5–13 (2005). https://doi.org/10.1007/s00401-004-0952-x

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