Abnormal synaptic architecture in iPSC-derived neurons from a multi-generational family with genetic Creutzfeldt-Jakob disease DOI Creative Commons

Aldana D. Gojanovich,

Nhat T. T. Le, Robert C.C. Mercer

et al.

Stem Cell Reports, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

The brain interactome of a permissive prion replication substrate DOI Creative Commons

Hamza Arshad,

Shehab Eid, Surabhi Mehra

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106802 - 106802

Published: Jan. 1, 2025

Bank voles are susceptible to prion strains from many different species, yet the molecular mechanisms underlying ability of bank vole protein (BVPrP) function as a universal acceptor remain unclear. Potential differences in environments and interaction networks on cell surface brain cells may contribute BVPrP's unusual behavior. To test this hypothesis, we generated knock-in mice that express physiological levels BVPrP (M109 isoform) employed mass spectrometry compare interactomes mouse (Mo) PrP following mild vivo crosslinking tissue. Substantial overlap was observed between top interactors for MoPrP, with established PrP-interactors such neural adhesion molecules, subunits Na

Language: Английский

Citations

1
Convergent generation of atypical prions in knockin mouse models of genetic prion disease DOI Creative Commons
Surabhi Mehra,

Matthew E.C. Bourkas,

Lech Kaczmarczyk

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(15)

Published: July 31, 2024

Most cases of human prion disease arise due to spontaneous misfolding WT or mutant protein, yet recapitulating this event in animal models has proven challenging. It remains unclear whether generation can occur within the mouse lifespan absence protein overexpression and how disease-causing mutations affect strain properties. To address these issues, we generated knockin mice that express misfolding-prone bank vole (BVPrP). While expressing BVPrP (I109 variant) remained free from neurological disease, a subset with (D178N E200K) causing genetic developed progressive illness. Brains spontaneously ill contained disease-specific neuropathological changes as well atypical protease-resistant BVPrP. Moreover, brain extracts D178N- E200K-mutant BVPrP-knockin exhibited seeding activity transmitted Surprisingly, properties prions appeared identical before after transmission, suggesting both guide formation similar strain. These findings imply develop bona fide diseases may share uniform initial mechanism action.

Language: Английский

Citations

6
Oxidative Stress and Mitochondrial Impairment: Key Drivers in Neurodegenerative Disorders DOI

Pei Wen,

Zhixin Sun,

Fengting Gou

et al.

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102667 - 102667

Published: Jan. 1, 2025

Language: Английский

Citations

0
Abnormal synaptic architecture in iPSC-derived neurons from a multi-generational family with genetic Creutzfeldt-Jakob disease DOI Creative Commons

Aldana D. Gojanovich,

Nhat T. T. Le, Robert C.C. Mercer

et al.

Stem Cell Reports, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

1