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@ARTICLE{Muschol:1017565,
author = {Muschol, Martin and Hoyer, Wolfgang},
title = {{A}myloid oligomers as on-pathway precursors or off-pathway
competitors of fibrils},
journal = {Frontiers in molecular biosciences},
volume = {10},
issn = {2296-889X},
address = {Lausanne},
publisher = {Frontiers},
reportid = {FZJ-2023-04205},
pages = {1120416},
year = {2023},
abstract = {Amyloid Diseases involve the growth of disease specific
proteins into amyloid fibrils and their deposition in
protein plaques. Amyloid fibril formation is typically
preceded by oligomeric intermediates. Despite significant
efforts, the specific role fibrils or oligomers play in the
etiology of any given amyloid disease remains controversial.
In neurodegenerative disease, though, amyloid oligomers are
widely considered critical contributors to disease symptoms.
Aside from oligomers as inevitable on-pathway precursors of
fibril formation, there is significant evidence for
off-pathway oligomer formation competing with fibril growth.
The distinct mechanisms and pathways of oligomer formation
directly affect our understanding under which conditions
oligomers emerge in vivo, and whether their formation is
directly coupled to, or distinct from, amyloid fibril
formation. In this review, we will discuss the basic energy
landscapes underlying the formation of on-pathway vs.
off-pathway oligomers, their relation to the related amyloid
aggregation kinetics, and their resulting implications for
disease etiology. We will review evidence on how differences
in the local environment of amyloid assembly can
dramatically shift the relative preponderance of oligomers
vs. fibrils. Finally, we will comment on gaps in our
knowledge of oligomer assembly, of their structure, and on
how to assess their relevance to disease etiology.},
cin = {IBI-7},
ddc = {570},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5244 - Information Processing in Neuronal Networks
(POF4-524)},
pid = {G:(DE-HGF)POF4-5244},
typ = {PUB:(DE-HGF)36 / PUB:(DE-HGF)16},
pubmed = {36845541},
UT = {WOS:000937088500001},
doi = {10.3389/fmolb.2023.1120416},
url = {https://juser.fz-juelich.de/record/1017565},
}