Trends in Cell Biology
Volume 26, Issue 8, August 2016, Pages 559-560
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Series: From the Archive
Ron R. Kopito: Unfolding the Secrets of Protein Aggregation

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What was known about protein aggregation at the time of writing this review?

Protein aggregation was not widely considered by cell biologists before the late 1990s. Prior to then, aggregation was thought about mainly by biochemists as a problem to be avoided during protein purification and by neuropathologists as morphological evidence of neurodegenerative disease pathology. Perhaps the most important development that brought the question of protein aggregation to the attention of cell biologists was the identification of genes that underlie dominantly inherited

How has the field evolved since this review?

The past 16 years have seen an explosion of studies focused on protein homeostasis and the cell biology of protein aggregation. Many different proteins and have been reported to form aggresomes or ⿿aggresome-like⿿ inclusions, although very few of these have been shown to be microtubule-dependent. Emerging data support a broader view of protein aggregation as an adaptive cellular response and not an exclusively pathogenic one. Functional intracellular protein deposits include structures

What is the future of the field and what outstanding questions remain?

The epidemic of age-related neurodegenerative diseases and their economic burden will continue to keep efforts at understanding the cell biology of protein aggregation at the forefront of research. Important questions that remain still include the ones that I outlined in my 2000 review. Does microtubule-dependent aggregate transport contribute to the formation and clearance of protein aggregates in neurons? How are substrates recognized/selected for delivery to aggresomes and other IBs? What is

What characteristics do you feel make a review valuable?

The most important features that make a review valuable are addressing compelling and timely questions and providing a conceptual framework around which to address controversial views.

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