| Structural highlights
Publication Abstract from PubMed
Misfolding and aggregation of disease-specific proteins, resulting in the formation of filamentous cellular inclusions, is a hallmark of neurodegenerative disease with characteristic filament structures, or conformers, defining each proteinopathy. Here we show that a previously unsolved amyloid fibril composed of a 135 amino acid C-terminal fragment of TMEM106B is a common finding in distinct human neurodegenerative diseases, including cases characterized by abnormal aggregation of TDP-43, tau, or alpha-synuclein protein. A combination of cryoelectron microscopy and mass spectrometry was used to solve the structures of TMEM106B fibrils at a resolution of 2.7 A from postmortem human brain tissue afflicted with frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP, n = 8), progressive supranuclear palsy (PSP, n = 2), or dementia with Lewy bodies (DLB, n = 1). The commonality of abundant amyloid fibrils composed of TMEM106B, a lysosomal/endosomal protein, to a broad range of debilitating human disorders indicates a shared fibrillization pathway that may initiate or accelerate neurodegeneration.
, PMID:35247328[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chang A, Xiang X, Wang J, Lee C, Arakhamia T, Simjanoska M, Wang C, Carlomagno Y, Zhang G, Dhingra S, Thierry M, Perneel J, Heeman B, Forgrave LM, DeTure M, DeMarco ML, Cook CN, Rademakers R, Dickson DW, Petrucelli L, Stowell MHB, Mackenzie IRA, Fitzpatrick AWP. Homotypic fibrillization of TMEM106B across diverse neurodegenerative diseases. Cell. 2022 Mar 1. pii: S0092-8674(22)00259-8. doi: 10.1016/j.cell.2022.02.026. PMID:35247328 doi:http://dx.doi.org/10.1016/j.cell.2022.02.026
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