Aggresomes, inclusion bodies and protein aggregation

RR Kopito - Trends in cell biology, 2000 - cell.com
Trends in cell biology, 2000cell.com
Intracellular and extracellular accumulation of aggregated protein are linked to many
diseases, including ageing-related neurodegeneration and systemic amyloidosis. Cells
avoid accumulating potentially toxic aggregates by mechanisms including the suppression
of aggregate formation by molecular chaperones and the degradation of misfolded proteins
by proteasomes. Once formed, aggregates tend to be refractory to proteolysis and to
accumulate in inclusion bodies. This accumulation has been assumed to be a diffusion …
Abstract
Intracellular and extracellular accumulation of aggregated protein are linked to many diseases, including ageing-related neurodegeneration and systemic amyloidosis. Cells avoid accumulating potentially toxic aggregates by mechanisms including the suppression of aggregate formation by molecular chaperones and the degradation of misfolded proteins by proteasomes. Once formed, aggregates tend to be refractory to proteolysis and to accumulate in inclusion bodies. This accumulation has been assumed to be a diffusion-limited process, but recent studies suggest that, in animal cells, aggregated proteins are specifically delivered to inclusion bodies by dynein-dependent retrograde transport on microtubules. This microtubule-dependent inclusion body is called an aggresome.
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