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@ARTICLE{Schwarz:294070,
author = {D. Schwarz and M. L. Marois and V. Sturm and A. S. Peters
and R. Longuespée$^*$ and D. Helm$^*$ and M. Schneider$^*$
and B. Eichmüller and A. S. Hidmark and M. Fischer and Z.
Kender and C. Schwab and I. Hausser and J. Weis and S.
Dihlmann and D. Böckler and M. Bendszus and S. Heiland and
S. Herzig and P. P. Nawroth and J. Szendroedi and T.
Fleming},
title = {{E}xploring {S}tructural and {M}olecular {F}eatures of
{S}ciatic {N}erve {L}esions in {D}iabetic {N}europathy:
{U}nveiling {P}athogenic {P}athways and {T}argets.},
journal = {Diabetes},
volume = {74},
number = {1},
issn = {0012-1797},
address = {Alexandria, Va},
publisher = {Assoc.},
reportid = {DKFZ-2024-02091},
pages = {65-74},
year = {2025},
note = {2025 Jan 1;74(1):65-74},
abstract = {Lesioned fascicles (LF) in the sciatic nerves of
individuals with diabetic neuropathy (DN) correlate with
clinical symptom severity. This study aimed to characterize
the structural and molecular composition of these lesions to
better understand DN pathogenesis. Sciatic nerves from
amputees with and without type 2 diabetes (T2D) were
examined using ex vivo magnetic resonance neurography, in
vitro imaging, and proteomic analysis. Lesions were only
found in T2D donors and exhibited significant structural
abnormalities, including axonal degeneration, demyelination,
and impaired blood nerve barrier (BNB). While non-lesioned
fascicles from T2D donors showed activation of
neuroprotective pathways, lesioned fascicles lacked this
response and instead displayed increased complement
activation via the classical pathway. The detection of
liver-derived acute-phase proteins suggests that BNB
disruption facilitates harmful inter-organ communication
between the liver and nerves. These findings reveal key
molecular mechanisms contributing to DN and highlight
potential targets for therapeutic intervention.},
cin = {B350 / HD01 / W120},
ddc = {610},
cid = {I:(DE-He78)B350-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)W120-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39418320},
doi = {10.2337/db24-0493},
url = {https://inrepo02.dkfz.de/record/294070},
}