SWATH Mass Spectrometry-Based CSF Proteome Profile of GBA-Linked Parkinson’s Disease Patients
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SWATH Mass Spectrometry-Based CSF Proteome Profile of GBA-Linked Parkinson’s Disease Patients. / Zafar, Saima; Noor, Aneeqa; Younas, Neelam; Shafiq, Mohsin; Schmitz, Matthias; Wurster, Isabel; Brockmann, Kathrin; Gasser, Thomas; Zerr, Inga.
In: INT J MOL SCI, Vol. 23, No. 22, 14166, 16.11.2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - SWATH Mass Spectrometry-Based CSF Proteome Profile of GBA-Linked Parkinson’s Disease Patients
AU - Zafar, Saima
AU - Noor, Aneeqa
AU - Younas, Neelam
AU - Shafiq, Mohsin
AU - Schmitz, Matthias
AU - Wurster, Isabel
AU - Brockmann, Kathrin
AU - Gasser, Thomas
AU - Zerr, Inga
PY - 2022/11/16
Y1 - 2022/11/16
N2 - 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.
AB - 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.
U2 - 10.3390/ijms232214166
DO - 10.3390/ijms232214166
M3 - SCORING: Journal article
C2 - 36430645
VL - 23
JO - INT J MOL SCI
JF - INT J MOL SCI
SN - 1661-6596
IS - 22
M1 - 14166
ER -