Open AccessAggregation Formation in the Polyglutamine Diseases: Protection at a Cost?
Author(s) -
Tiffany W. Todd,
Janghoo Lim
Publication year - 2013
Publication title -
molecules and cells/molecules and cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.665
H-Index - 79
eISSN - 0219-1032
pISSN - 1016-8478
DOI - 10.1007/s10059-013-0167-x
Subject(s) - protein aggregation , disease , neuroscience , pathogenesis , protein folding , medicine , biology , microbiology and biotechnology , immunology , pathology
Mutant protein aggregation is a hallmark of many neurodegenerative diseases, including the polyglutamine disorders. Although the correlation between aggregation formation and disease pathology originally suggested that the visible inclusions seen in patient tissue might directly contribute to pathology, additional studies failed to confirm this hypothesis. Current opinion in the field of polyglutamine disease research now favors a model in which large inclusions are cytoprotective and smaller oligomers or misfolded monomers underlie pathogenesis. Nonetheless, therapies aimed at reducing or preventing aggregation show promise. This review outlines the debate about the role of aggregation in the polyglutamine diseases as it has unfolded in the literature and concludes with a brief discussion on the manipulation of aggregation formation and clearance mechanisms as a means of therapeutic intervention.