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These expanded repeats produce polyglycine (polyG) proteins, and the accumulation of these polyG proteins in neuronal nuclei serves as the characteristic pathological hallmark of NIID. However, the native cellular ultrastructure of polyG and its contribution to pathology remain poorly understood. Here, using a transgenic NIID mouse model, we extract polyG assemblies from diseased brain and characterize their architecture by cryo\u2010electron tomography (cryo\u2010ET). We further examine their native organization by tracer\u2010guided in situ cryo\u2010ET in vitrified mouse brain. We find that polyG forms highly branched \u223c5 nm fibrils that laterally coalesce into densely packed ribbons, which represent the predominant polyG state within neuronal nuclei in situ. In parallel, proximity\u2010dependent labeling coupled to mass spectrometry reveals selective enrichment of proteostasis factors\u2014including proteasome subunits and molecular chaperones\u2014at polyG assemblies in mouse brain. Consistent with this, cryo\u2010ET visualizes proteasome\u2010like particles decorating ribbon\u2010shaped surfaces and edges in cells. Together, these findings uncover an unexpected ribbon\u2010shaped supramolecular architecture for a low\u2010complexity disease protein and suggest that nuclear polyG ribbons act as scaffolds that engage proteostasis machinery, providing mechanistic insight into NIID.\n                  <\/jats:p>","DOI":"10.1002\/advs.76630","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:57:21Z","timestamp":1784548641000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PolyG Fibrils Coalesce Into Nuclear Ribbons That Engage Proteostasis Machinery in Neuronal Intranuclear Inclusion Disease"],"prefix":"10.1002","volume":"13","author":[{"given":"Hui","family":"Dong","sequence":"first","affiliation":[{"name":"Interdisciplinary Research Center on Biology and Chemistry State Key Laboratory of Chemical Biology Shanghai Institute of Organic Chemistry Chinese Academy of Sciences  Shanghai 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