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Annual Review of Cell and Developmental Biology

Volume 36, 2020

Developing Therapies for Neurodegenerative Disorders: Insights from Protein Aggregation and Cellular Stress Responses

Abstract

As the world's population ages, neurodegenerative disorders are poised to become the commonest cause of death. Despite this, they remain essentially untreatable. Characterized pathologically both by the aggregation of disease-specific misfolded proteins and by changes in cellular stress responses, to date, therapeutic approaches have focused almost exclusively on reducing misfolded protein load—notably amyloid beta (Aβ) in Alzheimer's disease. The repeated failure of clinical trials has led to despondency over the possibility that these disorders will ever be treated. We argue that this is in fact a time for optimism: Targeting various generic stress responses is emerging as an increasingly promising means of modifying disease progression across these disorders. New treatments are approaching clinical trials, while novel means of targeting aggregates could eventually act preventively in early disease.

Keyword(s): autophagy, integrated stress response, neurodegenerative disease, neuroprotection, protein aggregation, therapy, unfolded protein response
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/content/journals/10.1146/annurev-cellbio-040320-120625
2020-10-06
2024-04-25
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/content/journals/10.1146/annurev-cellbio-040320-120625
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Developing Therapies for Neurodegenerative Disorders: Insights from Protein Aggregation and Cellular Stress Responses
Annual Review of Cell and Developmental Biology 36, 165 (2020); https://doi.org/10.1146/annurev-cellbio-040320-120625
/content/journals/10.1146/annurev-cellbio-040320-120625
/content/journals/10.1146/annurev-cellbio-040320-120625
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