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Translational NeuroscienceToward New Therapies$
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Karoly Nikolich and Steven E. Hyman

Print publication date: 2015

Print ISBN-13: 9780262029865

Published to MIT Press Scholarship Online: September 2016

DOI: 10.7551/mitpress/9780262029865.001.0001

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PRINTED FROM MIT PRESS SCHOLARSHIP ONLINE (www.mitpress.universitypressscholarship.com). (c) Copyright The MIT Press, 2022. All Rights Reserved. An individual user may print out a PDF of a single chapter of a monograph in MITSO for personal use.date: 24 June 2022

Neurodegenerative Diseases

Neurodegenerative Diseases

Where Are We Not Looking for Answers?

(p.59) 5 Neurodegenerative Diseases
Translational Neuroscience

Walter J. Koroshetz

Lennart Mucke

The MIT Press

As life expectancy increases, burden of illness soars. The growing magnitude of the health problem and numerous failed trials of agents once considered worth investment (e.g., Alzheimer, Parkinson, and Huntington diseases) demand critical examination. Neurodegeneratives diseases are more complicated than previously thought, and assumptions based on imperfect or incomplete information from animal models are flawed. There is, however, renewed optimism that science will be able to provide relief. This chapter considers existing scientific gaps in effective treatments for neurodegeneration. Discoveries that present tantalizing therapeutic hypotheses are viewed as pieces of a puzzle. At its core, neurodegeneration is a problem of cell health. Importantly, cells are interrelated within the brain, and thus study cannot be limited to one type of cell. Neurodegenerative diseases must be considered as disorders of nervous system circuits, with patients’ symptoms manifestations of neural circuit dysfunction. Successful treatment needs to normalize the biology within individual cells and tissue, and preserve or repair the information processing in important neural circuits. This places new biologic discoveries in perspective and promotes discussion of gaps that stand between discoveries and knowledge of neurodegeneration in overall tissues and circuit dysfunction that eventuates clinically.

Keywords:   Strüngmann Forum Reports, translational neuroscience, age-dependent neurodegeneration, Alzheimer, Parkinson, Huntington, neural circuit dysfunction, animal models

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