Combating neurodegenerative disease with chemical probes and model systems.

Abstract

The disheartening results of recent clinical trials for neurodegenerative disease (ND) therapeutics underscore the need for a more comprehensive understanding of the underlying disease biology before effective therapies can be devised. One hallmark of many NDs is a disruption in protein homeostasis. Therefore, investigating the role of protein homeostasis in these diseases is central to delineating their underlying pathobiology. Here, we review the seminal role that chemical biology has played in furthering the research on and treatment of dysfunctional protein homeostasis in NDs. We also discuss the vital and predictive role of model systems in identifying conserved homeostasis pathways and genes therein that are altered in neurodegeneration. Integrating approaches from chemical biology with the use of model systems yields a powerful toolkit with which to unravel the complexities of ND biology.

• Authors: Priyanka Narayan, Sepehr Ehsani, Susan Lindquist
• Journal: Nature chemical biology (Nat Chem Biol) Vol. 10 Issue 11 Pg. 911-20 (Nov 2014) ISSN: 1552-4469 [Electronic] United States
• PMID: 25325702 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Molecular Probes
• Proteins

Topics

• Animals
• Homeostasis (drug effects)
• Humans
• Models, Biological
• Molecular Probes (chemistry, pharmacology, therapeutic use)
• Neurodegenerative Diseases (drug therapy, metabolism)
• Proteins (antagonists & inhibitors, genetics, metabolism)