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Animal models of neurodegenerative diseases

Abstract

Animal models of adult-onset neurodegenerative diseases have enhanced the understanding of the molecular pathogenesis of Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Nevertheless, our understanding of these disorders and the development of mechanistically designed therapeutics can still benefit from more rigorous use of the models and from generation of animals that more faithfully recapitulate human disease. Here we review the current state of rodent models for Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis. We discuss the limitations and utility of current models, issues regarding translatability, and future directions for developing animal models of these human disorders.

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Acknowledgements

This work was supported by grants from the NIH/NINDS NS38377 Morris K. Udall Parkinson’s Disease Research Center, NIH/NINDS NS082205, NIH/NINDS NS098006, the JPB Foundation and Michael J. Fox Foundation. T.M.D. is supported by the Abramson Professorship. T.M.D. acknowledges joint participation by the Adrienne Helis Malvin Medical Research Foundation through its direct engagement in the continuous active conduct of medical research in conjunction with The Johns Hopkins Hospital, the Johns Hopkins University School of Medicine, and the Foundation’s Parkinson’s Disease Program M-1, M-2, M-2015. Supported by grants from the NIH to T.E.G. (P01CA166009, U01AG046139 R01AG018454, P50AG047266) and to C.L.T. (R01NS087227). C.L.-T. was supported by grants from the ALS Association, the Target ALS Foundation, ALS Finding a Cure, the Association Française contre les Myopathies, and the Pape Adams Charitable Foundation.

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Correspondence to Ted M. Dawson or Todd E. Golde or Clotilde Lagier-Tourenne.

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T.E.G. is a cofounder of Lacerta Inc. T.M.D. is a consultant and advisor to Sun Pharma Advanced Research Company Ltd. T.M.D. is a member of American Gene Technologies International Inc., advisory board and owns stock options in the company. T.M.D. is a consultant to Inhibikase Therapeutics and owns stock options in the company. T.M.D. is a founder of Valted, LLC and holds an ownership equity interest in the company. T.M.D. is an inventor of technology of Neuraly, Inc. that has optioned from Johns Hopkins University. T.M.D. is a founder of, and holds shares of stock options as well as equity in, Neuraly, Inc. All these arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict-of-interest policies.

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Dawson, T.M., Golde, T.E. & Lagier-Tourenne, C. Animal models of neurodegenerative diseases. Nat Neurosci 21, 1370–1379 (2018). https://doi.org/10.1038/s41593-018-0236-8

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