Amyotrophic Lateral Sclerosis (ALS) is a complex and incurable neurodegenerative disorder in whic... more Amyotrophic Lateral Sclerosis (ALS) is a complex and incurable neurodegenerative disorder in which genetic and epigenetic factors contribute to the pathogenesis of all forms of ALS. The interplay of genetic predisposition and environmental footprints generates epigenetic signatures in the cells of affected tissues, which then alter transcriptional programs. Epigenetic modifications that arise from genetic predisposition and systemic environmental footprints should in theory be detectable not only in affected CNS tissue but also in the periphery. Here, we identify an ALS-associated epigenetic signature (‘epiChromALS’) by chromatin accessibility analysis of blood cells of ALS patients. In contrast to the blood transcriptome signature, epiChromALS includes also genes that are not expressed in blood cells; it is enriched in CNS neuronal pathways and it is present in the ALS motor cortex. By combining simultaneous ATAC-seq and RNA-seq with single-cell sequencing in PBMCs and motor cortex...
Accumulating evidence suggests that microRNAs (miRNAs) are a contributing factor to neurodegenera... more Accumulating evidence suggests that microRNAs (miRNAs) are a contributing factor to neurodegenerative diseases. Although altered miRNA profiles in serum or plasma have been reported for several neurodegenerative diseases, little is known about the interaction between dysregulated miRNAs and their protein binding partners. We found significant alterations of the miRNA abundance pattern in serum and in isolated serum-derived extracellular vesicles of Parkinson’s disease (PD) patients. The differential expression of miRNA in PD patients was more robust in serum than in isolated extracellular vesicles and could separate PD patients from healthy controls in an unsupervised approach to a high degree. We identified a novel protein interaction partner for the strongly dysregulated hsa-mir-4745-5p. Our study provides further evidence for the involvement of miRNAs and HNF4a in PD. The demonstration that miRNA-protein binding might mediate the pathologic effects of HNF4a both by direct binding...
TAR DNA binding protein 43 (TDP-43) is closely related to the pathogenesis of amyotrophic lateral... more TAR DNA binding protein 43 (TDP-43) is closely related to the pathogenesis of amyotrophic lateral sclerosis (ALS) and translocates to stress granules (SGs). The role of SGs as aggregation-promoting “bioreactors” for TDP-43, however, is still under debate. We analyzed TDP-43 mobility and localization under different stress and recovery conditions using live cell single-molecule tracking and super-resolution microscopy. Besides reduced mobility within SGs, a stress induced decrease of TDP-43 mobility in the cytoplasm and the nucleus was observed. Stress removal led to a recovery of TDP-43 mobility, which strongly depended on the stress duration. ‘Stimulated-emission depletion microscopy’ (STED) and ‘tracking and localization microscopy’ (TALM) revealed not only TDP-43 substructures within stress granules but also numerous patches of slow TDP-43 species throughout the cytoplasm. The data provide new insights into the aggregation of TDP-43 in living cells and provide evidence suggesting...
Luciferase signal of S1/SOD1-2 and S2/SOD1-1 is not based on a nonspecific binding of luciferase ... more Luciferase signal of S1/SOD1-2 and S2/SOD1-1 is not based on a nonspecific binding of luciferase halves. (A) Luciferase activity measurement of living H4 cells and (B) conditioned medium 24 h post transfection with luciferase halves alone (L1 + L2) or luciferase halves tagged to α-synuclein and SOD1. Figure shows pooled data from 3 independent experiments after normalization to the respective mean of luciferase activity of co-transfected cells with L1 + L2 (two tailed, unpaired student's t-test, n = 12, * p
Co-IP studies confirm the α-synuclein-SOD1 binding. (A) α-Synuclein immunoprecipitation of co-tra... more Co-IP studies confirm the α-synuclein-SOD1 binding. (A) α-Synuclein immunoprecipitation of co-transfected H4 cells using α-synuclein antibody co-immunoprecipitated SOD1-myc and endogenous SOD1. Input: 5 μg. (B) Immunoprecipitation using myc antibody co-immunoprecipitated α-synuclein. After α-synuclein detection, membrane was incubated with stripping buffer, blocked and incubated with an anti-tau antibody and secondary antibody. (C) α-Synuclein immunoprecipitation of wt mouse brain homogenate without the usage of the DSP crosslinking reagent detects co-immunoprecipitated SOD1. Input: 8 μg. (TIF 4670 kb)
Co-localization of α-synuclein and SOD1 in wt mouse brain. Representative images of C57Bl/6 wt mo... more Co-localization of α-synuclein and SOD1 in wt mouse brain. Representative images of C57Bl/6 wt mouse brain sections co-immunostained for α-synuclein (Alexa 488, green) and SOD1 (Alexa 546, red). Nuclei were stained with DAPI. As control, sections were stained either with α-synuclein or SOD1 primary antibody but with both fluorophores (Alexa 488, Alexa 546) conjugated secondary antibodies. (TIF 7729 kb)
Concept of the extracellular complementation assay: Cells expressing proteins with n-terminal hal... more Concept of the extracellular complementation assay: Cells expressing proteins with n-terminal halve of hGluc or proteins with c-terminal halve of hGluc were lysed, followed by determination the concentrations α-synuclein and SOD1. Lysates were adjusted to the same molarity of α-synuclein or SOD1 and combined. After incubation, luciferase activity was measured. (TIF 2014 kb)
Increase in luciferase activity in presence of α-synuclein and reduced luciferase activity in abs... more Increase in luciferase activity in presence of α-synuclein and reduced luciferase activity in absence of α-synuclein does not derive from unequal expression levels. A Densitometry of western blots from H4 cell co-transfected with SOD1-1 /-2 complementation pair and with myc, wt, A30P or A53T α-synuclein. B Expression level of S1/S2 in the presence of myc, wt and mutated SOD1-myc relative to β-actin (two tailed, unpaired student's t-test, n = 3). (C) Expression level of SOD1-1 and SOD1-2 of lysates from scrambled-shRNA stabile H4 cell line and two α-synuclein-shRNA stabile H4 cell lines (α-syn I, α-syn II) relative to β-actin (two tailed, unpaired student's t-test, n = 4). (D) Densitometry of western blots from SOD1-1 and SOD1-2 co-transfected H4 cells treated with 7 μM recombinant α-synuclein or solvent PBS (two tailed, unpaired student's t-test, n = 3). (n.s. = not significant). (TIF 964 kb)
Amtierender Dekan: Prof. Dr. Klaus-Dieter Spindler Erstgutachter: apl. Prof. Dr. Wolfgang Weidema... more Amtierender Dekan: Prof. Dr. Klaus-Dieter Spindler Erstgutachter: apl. Prof. Dr. Wolfgang Weidemann Zweitgutachter:
Aggregation of alpha-synuclein (alpha-syn) has been linked to the pathogenesis of Parkinsons Dise... more Aggregation of alpha-synuclein (alpha-syn) has been linked to the pathogenesis of Parkinsons Disease (PD) and other neurodegenerative diseases. Increasing evidence suggests that prefibrillar oligomers and protofibrils, rather than mature fibrils of alpha-syn, are the pathogenic species in PD. Despite extensive effort on studying oligomerisation of alpha-syn, no studies have compared different oligomer species directly on a single particle level and investigated their biological effects on cells. In this study we applied a novel highly sensitive single molecule detection system that allowed a direct comparison of different oligomer types. Furthermore, we studied biological effects of different oligomer types on cells. For this purpose, we developed new oligomerisation protocols, that enabled the use of these different oligomers in cell culture. We found that all of our three aggregation protocols resulted in heterogeneous populations of oligomers. Some types of oligomers induced cell death via disruption of cellular ion homeostasis by a presumably pore-forming mechanism. Other oligomer types could directly enter the cell resulting in increased alpha-syn aggregation. Based on our results we propose that under various physiological conditions heterogeneous populations of oligomeric forms will co-exist in an equilibrium. These different oligomer types lead directly or indirectly to cell damage. Our data indicate that inhibition of early alpha-syn aggregation events would consequently prevent all alpha-syn oligomer related toxicities. This has important implications for the development of disease modifying drugs for the treatment of PD and other synucleinopathies.
Several age-related neurodegenerative disorders are associated with protein misfolding and aggreg... more Several age-related neurodegenerative disorders are associated with protein misfolding and aggregation of toxic peptides. α-synuclein (α-syn) aggregation and the resulting cytotoxicity is a hallmark of Parkinson's disease (PD) as well as dementia with Lewy bodies. Rising evidence points to oligomeric and pre-fibrillar forms as the pathogenic species, and oligomer secretion seems to be crucial for the spreading and progression of PD pathology. Recent studies implicate that dysfunctions in endolysosomal/autophagosomal pathways increase αsyn secretion. Mutation in the retromer-complex protein VPS35, which is involved in endosome to Golgi transport, was suggested to cause familial PD. GGA proteins regulate vesicular traffic between Golgi and endosomes and might work as antagonists for retromer complex mediated transport. To investigate the role of the GGAs in the α-syn oligomerization and/or secretion process we utilized protein-fragment complementation assays (PCA). We here demonstrate that GGAs alter α-syn oligomer secretion and α-syn oligomer-mediated toxicity. Specifically, we determined that GGA3 modifies extracellular α-syn species in an exosomeindependent manner. Our data suggest that GGA3 drives α-syn oligomerization in endosomal compartments and thus facilitates α-syn oligomer secretion. Preventing the early events in α-syn oligomer release may be a novel approach to halt disease spreading in PD and other synucleinopathies.
Biochemical and Biophysical Research Communications, 2011
Deposition of fibrillar α-synuclein as Lewy bodies is the neuropathological hallmark of Parkinson... more Deposition of fibrillar α-synuclein as Lewy bodies is the neuropathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Apart from α-synuclein, these intraneuronal inclusions contain over 250 different proteins. The actin binding protein gelsolin, has previously been suggested to be part of the Lewy body, but its potential role in α-synuclein aggregation remains unknown. Here, we studied the association between gelsolin and α-synuclein in brain tissue from PD and DLB patients as well as in a cell model for α-synuclein aggregation. Moreover, the potential effect of gelsolin on α-synuclein fibrillization was also investigated. Our data demonstrate that gelsolin co-occured with α-synuclein in Lewy bodies from affected human brain as well as with Lewy body-like inclusions in α-synuclein over expressing cells. Furthermore, in the presence of calcium chloride, gelsolin was found to enhance the aggregation rate of α-synuclein in vitro. Moreover, no apparent structural differences could be observed between fibrils formed in the presence or absence of gelsolin. Further studies on gelsolin and other Lewy body associated proteins are warranted to learn more about their potential role in the α-synuclein aggregation process.
Highlights d Inducible split protein mouse models to quantify a-synuclein oligomerization in vivo... more Highlights d Inducible split protein mouse models to quantify a-synuclein oligomerization in vivo d Aging promotes accumulation of size-defined a-synuclein oligomers d a-synuclein oligomerization takes place at the presynapse d Cell-to-cell transmission of a-synuclein is demonstrated in an intact mouse brain
The dysregulation of peripheral immunity in Parkinson’s Disease (PD) includes changes in both the... more The dysregulation of peripheral immunity in Parkinson’s Disease (PD) includes changes in both the relative numbers and gene expression of T cells. The presence of peripheral T-cell abnormalities in PD is well-documented, but less is known about their association to clinical parameters, such as age, age of onset, progression rate or severity of the disease. We took a detailed look at T-cell numbers, gene expression and activation in cross-sectional cohorts of PD patients and age-matched healthy controls by means of flow cytometry and NanoString gene expression assay. We show that the well-pronounced decrease in relative T-cell numbers in PD blood is mostly driven by a decrease of CD8+ cytotoxic T cells and is primarily associated with the severity of the disease. In addition, we demonstrate that the expression of inflammatory genes in T cells from PD patients is also associated with disease severity. PD T cells presented with increased activation upon stimulation with phytohemaggluti...
Alpha-synuclein and Cu, Zn superoxide dismutase (SOD1) are both aggregation-prone proteins that a... more Alpha-synuclein and Cu, Zn superoxide dismutase (SOD1) are both aggregation-prone proteins that are associated with Parkinson´s disease (PD) and amyotrophic lateral sclerosis (ALS), respectively. Recently, we showed that alpha-synuclein interacts with SOD1 in various cell types and tissues. Using a cell culture model, we also found that alpha-synuclein nucleates the polymerization of SOD1. Here, we discuss the current literature regarding their interaction and their co-localization in aggregates of human post-mortem tissue. Furthermore we comment on the reported alpha-synuclein-induced SOD1 polymerization in terms of cross-seeding effects in neurodegeneration.
Amyotrophic Lateral Sclerosis (ALS) is a complex and incurable neurodegenerative disorder in whic... more Amyotrophic Lateral Sclerosis (ALS) is a complex and incurable neurodegenerative disorder in which genetic and epigenetic factors contribute to the pathogenesis of all forms of ALS. The interplay of genetic predisposition and environmental footprints generates epigenetic signatures in the cells of affected tissues, which then alter transcriptional programs. Epigenetic modifications that arise from genetic predisposition and systemic environmental footprints should in theory be detectable not only in affected CNS tissue but also in the periphery. Here, we identify an ALS-associated epigenetic signature (‘epiChromALS’) by chromatin accessibility analysis of blood cells of ALS patients. In contrast to the blood transcriptome signature, epiChromALS includes also genes that are not expressed in blood cells; it is enriched in CNS neuronal pathways and it is present in the ALS motor cortex. By combining simultaneous ATAC-seq and RNA-seq with single-cell sequencing in PBMCs and motor cortex...
Accumulating evidence suggests that microRNAs (miRNAs) are a contributing factor to neurodegenera... more Accumulating evidence suggests that microRNAs (miRNAs) are a contributing factor to neurodegenerative diseases. Although altered miRNA profiles in serum or plasma have been reported for several neurodegenerative diseases, little is known about the interaction between dysregulated miRNAs and their protein binding partners. We found significant alterations of the miRNA abundance pattern in serum and in isolated serum-derived extracellular vesicles of Parkinson’s disease (PD) patients. The differential expression of miRNA in PD patients was more robust in serum than in isolated extracellular vesicles and could separate PD patients from healthy controls in an unsupervised approach to a high degree. We identified a novel protein interaction partner for the strongly dysregulated hsa-mir-4745-5p. Our study provides further evidence for the involvement of miRNAs and HNF4a in PD. The demonstration that miRNA-protein binding might mediate the pathologic effects of HNF4a both by direct binding...
TAR DNA binding protein 43 (TDP-43) is closely related to the pathogenesis of amyotrophic lateral... more TAR DNA binding protein 43 (TDP-43) is closely related to the pathogenesis of amyotrophic lateral sclerosis (ALS) and translocates to stress granules (SGs). The role of SGs as aggregation-promoting “bioreactors” for TDP-43, however, is still under debate. We analyzed TDP-43 mobility and localization under different stress and recovery conditions using live cell single-molecule tracking and super-resolution microscopy. Besides reduced mobility within SGs, a stress induced decrease of TDP-43 mobility in the cytoplasm and the nucleus was observed. Stress removal led to a recovery of TDP-43 mobility, which strongly depended on the stress duration. ‘Stimulated-emission depletion microscopy’ (STED) and ‘tracking and localization microscopy’ (TALM) revealed not only TDP-43 substructures within stress granules but also numerous patches of slow TDP-43 species throughout the cytoplasm. The data provide new insights into the aggregation of TDP-43 in living cells and provide evidence suggesting...
Luciferase signal of S1/SOD1-2 and S2/SOD1-1 is not based on a nonspecific binding of luciferase ... more Luciferase signal of S1/SOD1-2 and S2/SOD1-1 is not based on a nonspecific binding of luciferase halves. (A) Luciferase activity measurement of living H4 cells and (B) conditioned medium 24 h post transfection with luciferase halves alone (L1 + L2) or luciferase halves tagged to α-synuclein and SOD1. Figure shows pooled data from 3 independent experiments after normalization to the respective mean of luciferase activity of co-transfected cells with L1 + L2 (two tailed, unpaired student's t-test, n = 12, * p
Co-IP studies confirm the α-synuclein-SOD1 binding. (A) α-Synuclein immunoprecipitation of co-tra... more Co-IP studies confirm the α-synuclein-SOD1 binding. (A) α-Synuclein immunoprecipitation of co-transfected H4 cells using α-synuclein antibody co-immunoprecipitated SOD1-myc and endogenous SOD1. Input: 5 μg. (B) Immunoprecipitation using myc antibody co-immunoprecipitated α-synuclein. After α-synuclein detection, membrane was incubated with stripping buffer, blocked and incubated with an anti-tau antibody and secondary antibody. (C) α-Synuclein immunoprecipitation of wt mouse brain homogenate without the usage of the DSP crosslinking reagent detects co-immunoprecipitated SOD1. Input: 8 μg. (TIF 4670 kb)
Co-localization of α-synuclein and SOD1 in wt mouse brain. Representative images of C57Bl/6 wt mo... more Co-localization of α-synuclein and SOD1 in wt mouse brain. Representative images of C57Bl/6 wt mouse brain sections co-immunostained for α-synuclein (Alexa 488, green) and SOD1 (Alexa 546, red). Nuclei were stained with DAPI. As control, sections were stained either with α-synuclein or SOD1 primary antibody but with both fluorophores (Alexa 488, Alexa 546) conjugated secondary antibodies. (TIF 7729 kb)
Concept of the extracellular complementation assay: Cells expressing proteins with n-terminal hal... more Concept of the extracellular complementation assay: Cells expressing proteins with n-terminal halve of hGluc or proteins with c-terminal halve of hGluc were lysed, followed by determination the concentrations α-synuclein and SOD1. Lysates were adjusted to the same molarity of α-synuclein or SOD1 and combined. After incubation, luciferase activity was measured. (TIF 2014 kb)
Increase in luciferase activity in presence of α-synuclein and reduced luciferase activity in abs... more Increase in luciferase activity in presence of α-synuclein and reduced luciferase activity in absence of α-synuclein does not derive from unequal expression levels. A Densitometry of western blots from H4 cell co-transfected with SOD1-1 /-2 complementation pair and with myc, wt, A30P or A53T α-synuclein. B Expression level of S1/S2 in the presence of myc, wt and mutated SOD1-myc relative to β-actin (two tailed, unpaired student's t-test, n = 3). (C) Expression level of SOD1-1 and SOD1-2 of lysates from scrambled-shRNA stabile H4 cell line and two α-synuclein-shRNA stabile H4 cell lines (α-syn I, α-syn II) relative to β-actin (two tailed, unpaired student's t-test, n = 4). (D) Densitometry of western blots from SOD1-1 and SOD1-2 co-transfected H4 cells treated with 7 μM recombinant α-synuclein or solvent PBS (two tailed, unpaired student's t-test, n = 3). (n.s. = not significant). (TIF 964 kb)
Amtierender Dekan: Prof. Dr. Klaus-Dieter Spindler Erstgutachter: apl. Prof. Dr. Wolfgang Weidema... more Amtierender Dekan: Prof. Dr. Klaus-Dieter Spindler Erstgutachter: apl. Prof. Dr. Wolfgang Weidemann Zweitgutachter:
Aggregation of alpha-synuclein (alpha-syn) has been linked to the pathogenesis of Parkinsons Dise... more Aggregation of alpha-synuclein (alpha-syn) has been linked to the pathogenesis of Parkinsons Disease (PD) and other neurodegenerative diseases. Increasing evidence suggests that prefibrillar oligomers and protofibrils, rather than mature fibrils of alpha-syn, are the pathogenic species in PD. Despite extensive effort on studying oligomerisation of alpha-syn, no studies have compared different oligomer species directly on a single particle level and investigated their biological effects on cells. In this study we applied a novel highly sensitive single molecule detection system that allowed a direct comparison of different oligomer types. Furthermore, we studied biological effects of different oligomer types on cells. For this purpose, we developed new oligomerisation protocols, that enabled the use of these different oligomers in cell culture. We found that all of our three aggregation protocols resulted in heterogeneous populations of oligomers. Some types of oligomers induced cell death via disruption of cellular ion homeostasis by a presumably pore-forming mechanism. Other oligomer types could directly enter the cell resulting in increased alpha-syn aggregation. Based on our results we propose that under various physiological conditions heterogeneous populations of oligomeric forms will co-exist in an equilibrium. These different oligomer types lead directly or indirectly to cell damage. Our data indicate that inhibition of early alpha-syn aggregation events would consequently prevent all alpha-syn oligomer related toxicities. This has important implications for the development of disease modifying drugs for the treatment of PD and other synucleinopathies.
Several age-related neurodegenerative disorders are associated with protein misfolding and aggreg... more Several age-related neurodegenerative disorders are associated with protein misfolding and aggregation of toxic peptides. α-synuclein (α-syn) aggregation and the resulting cytotoxicity is a hallmark of Parkinson's disease (PD) as well as dementia with Lewy bodies. Rising evidence points to oligomeric and pre-fibrillar forms as the pathogenic species, and oligomer secretion seems to be crucial for the spreading and progression of PD pathology. Recent studies implicate that dysfunctions in endolysosomal/autophagosomal pathways increase αsyn secretion. Mutation in the retromer-complex protein VPS35, which is involved in endosome to Golgi transport, was suggested to cause familial PD. GGA proteins regulate vesicular traffic between Golgi and endosomes and might work as antagonists for retromer complex mediated transport. To investigate the role of the GGAs in the α-syn oligomerization and/or secretion process we utilized protein-fragment complementation assays (PCA). We here demonstrate that GGAs alter α-syn oligomer secretion and α-syn oligomer-mediated toxicity. Specifically, we determined that GGA3 modifies extracellular α-syn species in an exosomeindependent manner. Our data suggest that GGA3 drives α-syn oligomerization in endosomal compartments and thus facilitates α-syn oligomer secretion. Preventing the early events in α-syn oligomer release may be a novel approach to halt disease spreading in PD and other synucleinopathies.
Biochemical and Biophysical Research Communications, 2011
Deposition of fibrillar α-synuclein as Lewy bodies is the neuropathological hallmark of Parkinson... more Deposition of fibrillar α-synuclein as Lewy bodies is the neuropathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Apart from α-synuclein, these intraneuronal inclusions contain over 250 different proteins. The actin binding protein gelsolin, has previously been suggested to be part of the Lewy body, but its potential role in α-synuclein aggregation remains unknown. Here, we studied the association between gelsolin and α-synuclein in brain tissue from PD and DLB patients as well as in a cell model for α-synuclein aggregation. Moreover, the potential effect of gelsolin on α-synuclein fibrillization was also investigated. Our data demonstrate that gelsolin co-occured with α-synuclein in Lewy bodies from affected human brain as well as with Lewy body-like inclusions in α-synuclein over expressing cells. Furthermore, in the presence of calcium chloride, gelsolin was found to enhance the aggregation rate of α-synuclein in vitro. Moreover, no apparent structural differences could be observed between fibrils formed in the presence or absence of gelsolin. Further studies on gelsolin and other Lewy body associated proteins are warranted to learn more about their potential role in the α-synuclein aggregation process.
Highlights d Inducible split protein mouse models to quantify a-synuclein oligomerization in vivo... more Highlights d Inducible split protein mouse models to quantify a-synuclein oligomerization in vivo d Aging promotes accumulation of size-defined a-synuclein oligomers d a-synuclein oligomerization takes place at the presynapse d Cell-to-cell transmission of a-synuclein is demonstrated in an intact mouse brain
The dysregulation of peripheral immunity in Parkinson’s Disease (PD) includes changes in both the... more The dysregulation of peripheral immunity in Parkinson’s Disease (PD) includes changes in both the relative numbers and gene expression of T cells. The presence of peripheral T-cell abnormalities in PD is well-documented, but less is known about their association to clinical parameters, such as age, age of onset, progression rate or severity of the disease. We took a detailed look at T-cell numbers, gene expression and activation in cross-sectional cohorts of PD patients and age-matched healthy controls by means of flow cytometry and NanoString gene expression assay. We show that the well-pronounced decrease in relative T-cell numbers in PD blood is mostly driven by a decrease of CD8+ cytotoxic T cells and is primarily associated with the severity of the disease. In addition, we demonstrate that the expression of inflammatory genes in T cells from PD patients is also associated with disease severity. PD T cells presented with increased activation upon stimulation with phytohemaggluti...
Alpha-synuclein and Cu, Zn superoxide dismutase (SOD1) are both aggregation-prone proteins that a... more Alpha-synuclein and Cu, Zn superoxide dismutase (SOD1) are both aggregation-prone proteins that are associated with Parkinson´s disease (PD) and amyotrophic lateral sclerosis (ALS), respectively. Recently, we showed that alpha-synuclein interacts with SOD1 in various cell types and tissues. Using a cell culture model, we also found that alpha-synuclein nucleates the polymerization of SOD1. Here, we discuss the current literature regarding their interaction and their co-localization in aggregates of human post-mortem tissue. Furthermore we comment on the reported alpha-synuclein-induced SOD1 polymerization in terms of cross-seeding effects in neurodegeneration.
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Papers by Karin Danzer