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Amyloid oligomers: dynamics and toxicity in the cytosol and nucleus
Author(s) -
Kitamura Akira,
Kubota Hiroshi
Publication year - 2010
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2010.07570.x
Subject(s) - fluorescence recovery after photobleaching , cytosol , protein aggregation , photobleaching , chemistry , biophysics , neurodegeneration , förster resonance energy transfer , protein folding , amyloid (mycology) , biochemistry , nucleus , fluorescence , microbiology and biotechnology , biology , medicine , inorganic chemistry , physics , disease , pathology , quantum mechanics , membrane , enzyme
The accumulation of misfolded proteins in the cytosol and nucleus of neuronal cells leads to neurodegenerative disorders. Polyglutamine diseases are caused by polyglutamine‐expanded proteins, whereas mutations in superoxide dismutase 1 lead to amyotrophic lateral sclerosis. These structurally unstable mutant species perturb essential interactions between normal proteins and tend to aggregate because of the presence of exposed hydrophobic surfaces. Accumulating evidence suggests that soluble species, including misfolded monomers and oligomers, are more toxic than large insoluble aggregates or inclusions. Spectroscopic analysis, including fluorescence recovery after photobleaching and fluorescence loss in photobleaching, in living cells revealed that protein aggregates of misfolded proteins are dynamic structures that interact with other proteins, such as molecular chaperones. Fluorescence correlation spectroscopy analysis detected soluble oligomers/aggregates of misfolded proteins in cell extracts. Fluorescence resonance energy transfer analysis supported the notion that soluble oligomers/aggregates are formed before the formation of inclusions in vivo . Here, we reviewed the characteristics of oligomers and aggregates of misfolded proteins, with a particular focus on those revealed by spectroscopic analysis, and discussed how these oligomers may be toxic to cells.