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@ARTICLE{Zafar:165626,
author = {Zafar, Saima and Noor, Aneeqa and Younas, Neelam and
Shafiq, Mohsin and Schmitz, Matthias and Wurster, Isabel and
Brockmann, Kathrin and Gasser, Thomas and Zerr, Inga},
title = {{SWATH} {M}ass {S}pectrometry-{B}ased {CSF} {P}roteome
{P}rofile of {GBA}-{L}inked {P}arkinson's {D}isease
{P}atients.},
journal = {International journal of molecular sciences},
volume = {23},
number = {22},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {DZNE-2022-01759},
pages = {14166},
year = {2022},
abstract = {β-glucocerebrosidase (GBA)-associated mutations are a
significant risk factor for Parkinson's disease (PD) that
aggravate the disease pathology by upregulating the
deposition of α-Synuclein (α-Syn). The resultant clinical
profile varies for PD patients without GBA mutations. The
current study aimed to identify the proteomic targets
involved in the pathogenic pathways leading to the
differential clinical presentation of GBA-associated PD. CSF
samples (n = 32) were obtained from PD patients with GBA
mutations (n = 22), PD patients without GBA mutations (n =
7), and healthy controls that were carriers of GBA mutations
(n = 3). All samples were subjected to in-gel tryptic
digestion followed by the construction of the spectral
library and quantitative SWATH-based analysis. CSF α-Syn
levels were reduced in both PDIdiopathic and PDGBA cases.
Our SWATH-based mass spectrometric analysis detected 363
proteins involved in immune response, stress response, and
cell signaling in various groups. Intergroup analysis showed
that 52 proteins were significantly up- or downregulated in
various groups. Of these 52 targets, 20 proteins were
significantly altered in PDGBA cases only while 2 showed
different levels in PDIdiopathic patients. Our results show
that the levels of several pathologically relevant proteins,
including Contactin-1, Selenium-binding protein 1, Adhesion
G Protein-Coupled Receptor, and Apolipoprotein E are
significantly different among the sporadic and genetic
variants of PD and hint at aggravated synaptic damage,
oxidative stress, neuronal loss, and aggregation of α-Syn
in PDGBA cases.},
keywords = {Glucosylceramidase: metabolism / Humans /
Glucosylceramidase: genetics / Proteome / Parkinson Disease:
genetics / Proteomics / Mass Spectrometry / Parkinson
Disease: metabolism / Cerebrospinal Fluid: chemistry /
Cerebrospinal Fluid: metabolism / α-synuclein (Other) / CSF
(Other) / SWATH (Other) / proteomics (Other) / α-synuclein
(Other) / β-glucocerebrosidase (Other) / Glucosylceramidase
(NLM Chemicals) / Proteome (NLM Chemicals) /
β-glucocerebrosidase (Other)},
cin = {AG Zerr / Ext UMG Zerr / AG Gasser},
ddc = {540},
cid = {I:(DE-2719)1440011-1 / I:(DE-2719)5000037 /
I:(DE-2719)1210000},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC9699576},
pubmed = {pmid:36430645},
doi = {10.3390/ijms232214166},
url = {https://pub.dzne.de/record/165626},
}