title: 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.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Narayan
authors.affiliation: 1] Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA. [2] Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Sepehr
authors.identifier: 0000000296136898
authors.initials: S
authors.lastname: Ehsani
authors.affiliation: 1] Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA. [2] Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Lindquist
mesh_terms: D000818:Animals; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D015335:Molecular Probes / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D015335:Molecular Probes; D011506:Proteins