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The thermodynamics of neurodegenerative disease.

Accepted version
Peer-reviewed

Type

Article

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Abstract

The formation of protein aggregates in the brain is a central aspect of the pathology of many neurodegenerative diseases. This self-assembly of specific proteins into filamentous aggregates, or fibrils, is a fundamental biophysical process that can easily be reproduced in the test tube. However, it has been difficult to obtain a clear picture of how the biophysical insights thus obtained can be applied to the complex, multi-factorial diseases and what this means for therapeutic strategies. While new, disease-modifying therapies are now emerging, for the most devastating disorders, such as Alzheimer's and Parkinson's disease, they still fall well short of offering a cure, and few drug design approaches fully exploit the wealth of mechanistic insights that has been obtained in biophysical studies. Here, I attempt to provide a new perspective on the role of protein aggregation in disease, by phrasing the problem in terms of a system that, under constant energy consumption, attempts to maintain a healthy, aggregate-free state against the thermodynamic driving forces that inexorably push it toward pathological aggregation.

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Keywords

3101 Biochemistry and Cell Biology, 31 Biological Sciences, Alzheimer's Disease, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Neurodegenerative, Brain Disorders, Aging, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, Neurological

Journal Title

Biophys Rev (Melville)

Conference Name

Journal ISSN

2688-4089
2688-4089

Volume Title

5

Publisher

AIP Publishing