Proteostasis

Gumming up the works

See allHide authors and affiliations

Science  09 Mar 2018:
Vol. 359, Issue 6380, pp. 1115
DOI: 10.1126/science.359.6380.1115-a

Poly-GA aggregate within a neuron

CREDIT: Q. GUO ET AL., CELL 172, 696 (2018)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that has been linked to toxic aggregates of poly-Gly-Ala (poly-GA) peptides generated by aberrant translation of an expanded nucleotide repeat sequence. Proteasomes are cytosolic molecular machines involved in the degradation of misfolded and aggregated proteins. Guo et al. used cryo–electron tomography to examine the molecular architecture of poly-GA aggregates in situ in intact neurons. The peptide aggregates formed twisted ribbons that clumped together and that were surrounded by proteasomes trapped in their normally transient substrate-processing conformation. The extent of proteasome accumulation was such that the ability of the remaining proteasomes within the neuron to perform their normal housekeeping functions was likely to be impaired, potentially explaining the neuronal pathologies observed in ALS.

Cell 172, 696 (2018).

Navigate This Article