Cysteine-rich granulin-3 rapidly promotes amyloid-β fibrils in both redox states.

ABSTRACT: Granulins (GRNs 1-7) are cysteine-rich proteolytic products of progranulin (PGRN) that have recently been implicated in neurodegenerative diseases including frontotemporal dementia (FTD) and Alzheimer's disease (AD). Their precise mechanism in these pathologies remains uncertain, but both inflammatory and lysosomal roles have been observed for GRNs. Among the seven GRNs, GRN-3 is well characterized and is implicated within the context of FTD. However, the relationship between GRN-3 and amyloid-β (Aβ), a protein relevant in AD pathology, has not yet been explored. To gain insight into this mechanism, we investigated the effect of both oxidized and reduced GRN-3 on Aβ aggregation and found that both GRN-3 (oxidized) and rGRN-3 (reduced) bind to monomeric and oligomeric Aβ42 to promote rapid

SUBMITTER: Bhopatkar AA 

PROVIDER: S-EPMC6647844 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature