TY  - JOUR
A1  - Wulf, Maximilian
A1  - Barkovits, Katalin
A1  - Schork, Karin
A1  - Eisenacher, Martin
A1  - Riederer, Peter
A1  - Gerlach, Manfred
A1  - Eggers, Britta
A1  - Marcus, Katrin
T1  - The proteome of neuromelanin granules in dementia with Lewy bodies
JF  - Cells
N2  - Neuromelanin granules (NMGs) are organelle-like structures present in the human substantia nigra pars compacta. In addition to neuromelanin, NMGs contain proteins, lipids and metals. As NMG-containing dopaminergic neurons are preferentially lost in Parkinson’s disease and dementia with Lewy bodies (DLB), it is assumed that NMGs may play a role in neurodegenerative processes. Until now, this role is not completely understood and needs further investigation. We therefore set up an exploratory proteomic study to identify differences in the proteomic profile of NMGs from DLB patients (n = 5) compared to healthy controls (CTRL, n = 5). We applied a laser microdissection and mass-spectrometry-based approach, in which we used targeted mass spectrometric experiments for validation. In NMG-surrounding (SN\(_{Surr.}\)) tissue of DLB patients, we found evidence for ongoing oxidative damage and an impairment of protein degradation. As a potentially disease-related mechanism, we found α-synuclein and protein S100A9 to be enriched in NMGs of DLB cases, while the abundance of several ribosomal proteins was significantly decreased. As S100A9 is known to be able to enhance the formation of toxic α-synuclein fibrils, this finding points towards an involvement of NMGs in pathogenesis, however the exact role of NMGs as either neuroprotective or neurotoxic needs to be further investigated. Nevertheless, our study provides evidence for an impairment of protein degradation, ongoing oxidative damage and accumulation of potentially neurotoxic protein aggregates to be central mechanisms of neurodegeneration in DLB.
KW  - neuromelanin granules
KW  - neurodegeneration
KW  - dementia with Lewy bodies
KW  - proteomics
KW  - stress granules
KW  - substantia nigra pars compacta
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297465
SN  - 2073-4409
VL  - 11
IS  - 22
ER  - 
TY  - JOUR
A1  - Kline, Rachel A.
A1  - Lößlein, Lena
A1  - Kurian, Dominic
A1  - Aguilar Martí, Judit
A1  - Eaton, Samantha L.
A1  - Court, Felipe A.
A1  - Gillingwater, Thomas H.
A1  - Wishart, Thomas M.
T1  - An optimized comparative proteomic approach as a tool in neurodegenerative disease research
JF  - Cells
N2  - Recent advances in proteomic technologies now allow unparalleled assessment of the molecular composition of a wide range of sample types. However, the application of such technologies and techniques should not be undertaken lightly. Here, we describe why the design of a proteomics experiment itself is only the first step in yielding high-quality, translatable results. Indeed, the effectiveness and/or impact of the majority of contemporary proteomics screens are hindered not by commonly considered technical limitations such as low proteome coverage but rather by insufficient analyses. Proteomic experimentation requires a careful methodological selection to account for variables from sample collection, through to database searches for peptide identification to standardised post-mass spectrometry options directed analysis workflow, which should be adjusted for each study, from determining when and how to filter proteomic data to choosing holistic versus trend-wise analyses for biologically relevant patterns. Finally, we highlight and discuss the difficulties inherent in the modelling and study of the majority of progressive neurodegenerative conditions. We provide evidence (in the context of neurodegenerative research) for the benefit of undertaking a comparative approach through the application of the above considerations in the alignment of publicly available pre-existing data sets to identify potential novel regulators of neuronal stability.
KW  - proteomics
KW  - systems biology
KW  - experimental design
KW  - neurodegeneration
KW  - pathway analysis
KW  - data filtering
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285912
SN  - 2073-4409
VL  - 11
IS  - 17
ER  -