title: Structural disorder and the loss of RNA homeostasis in aging and neurodegenerative disease.
abstract: Whereas many cases of neurodegenerative disease feature the abnormal accumulation of protein, an abundance of recent literature highlights loss of RNA homeostasis as a ubiquitous and central feature of pathological states. In some diseases expanded repeats have been identified in non-coding regions of disease-associated transcripts, calling into question the relevance of protein in the disease mechanism. We review the literature in support of a hypothesis that intrinsically disordered proteins (proteins that lack a stable three dimensional conformation) are particularly sensitive to an age-related decline in maintenance of protein homeostasis. The potential consequences for structurally disordered RNA-binding proteins are explored, including their aggregation into complexes that could be transmitted through a prion-like mechanism. We propose that the spread of ribonucleoprotein complexes through the nervous system could propagate a neuronal error catastrophe at the level of RNA metabolism.
authors: Centre for Cancer Therapeutics, Ottawa Hospital Research Institute Ottawa, ON, Canada ; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa Ottawa, ON, Canada.
authors: Douglas A
authors: DA
authors: Gray
authors: John
authors: J
authors: Woulfe
keywords: RNA-binding proteins; aggregation; intrinsic disorder; neurodegeneration; proteasome
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