| 1. |
- Uhlén, Mathias, et al.
(författare)
-
The human secretome
- 2019
-
Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 12:609
-
Tidskriftsartikel (refereegranskat)abstract
- The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood.
|
|
| 2. |
- Häggmark, Anna, et al.
(författare)
-
Plasma profiling revelas three proteins associated to amyotrophic lateral sclerosis
- 2014
-
Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 1:8, s. 544-553
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is the most common adult motor neuron disease leading to muscular paralysis and death within 3-5 years from onset. Currently, there are no reliable and sensitive markers able to substantially shorten the diagnosis delay. The objective of the study was to analyze a large number of proteins in plasma from patients with various clinical phenotypes of ALS in search for novel proteins or protein profiles that could serve as potential indicators of disease.METHODS: Affinity proteomics in the form of antibody suspension bead arrays were applied to profile plasma samples from 367 ALS patients and 101 controls. The plasma protein content was directly labeled and protein profiles obtained using 352 antibodies from the Human Protein Atlas targeting 278 proteins. A focused bead array was then built to further profile eight selected protein targets in all available samples.RESULTS: Disease-associated significant differences were observed and replicated for profiles from antibodies targeting the proteins: neurofilament medium polypeptide (NEFM), solute carrier family 25 (SLC25A20), and regulator of G-protein signaling 18 (RGS18).INTERPRETATION: Upon further validation in several independent cohorts with inclusion of a broad range of other neurological disorders as controls, the alterations of these three protein profiles in plasma could potentially provide new molecular markers of disease that contribute to the quest of understanding ALS pathology.
|
|
| 3. |
- Månberg, Anna, 1985-, et al.
(författare)
-
Altered perivascular fibroblast activity precedes ALS disease onset
- 2021
-
Ingår i: Nature Medicine. - : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 27:4, s. 640-646
-
Tidskriftsartikel (refereegranskat)abstract
- Apart from well-defined factors in neuronal cells1, only a few reports consider that the variability of sporadic amyotrophic lateral sclerosis (ALS) progression can depend on less-defined contributions from glia2,3 and blood vessels4. In this study we use an expression-weighted cell-type enrichment method to infer cell activity in spinal cord samples from patients with sporadic ALS and mouse models of this disease. Here we report that patients with sporadic ALS present cell activity patterns consistent with two mouse models in which enrichments of vascular cell genes preceded microglial response. Notably, during the presymptomatic stage, perivascular fibroblast cells showed the strongest gene enrichments, and their marker proteins SPP1 and COL6A1 accumulated in enlarged perivascular spaces in patients with sporadic ALS. Moreover, in plasma of 574 patients with ALS from four independent cohorts, increased levels of SPP1 at disease diagnosis repeatedly predicted shorter survival with stronger effect than the established risk factors of bulbar onset or neurofilament levels in cerebrospinal fluid. We propose that the activity of the recently discovered perivascular fibroblast can predict survival of patients with ALS and provide a new conceptual framework to re-evaluate definitions of ALS etiology.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Remnestål, Julia, et al.
(författare)
-
Association of CSF proteins with tau and amyloid beta levels in asymptomatic 70-year-olds
- 2021
-
Ingår i: Alzheimer's Research & Therapy. - : BMC. - 1758-9193. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Increased knowledge of the evolution of molecular changes in neurodegenerative disorders such as Alzheimer's disease (AD) is important for the understanding of disease pathophysiology and also crucial to be able to identify and validate disease biomarkers. While several biological changes that occur early in the disease development have already been recognized, the need for further characterization of the pathophysiological mechanisms behind AD still remains. Methods In this study, we investigated cerebrospinal fluid (CSF) levels of 104 proteins in 307 asymptomatic 70-year-olds from the H70 Gothenburg Birth Cohort Studies using a multiplexed antibody- and bead-based technology. Results The protein levels were first correlated with the core AD CSF biomarker concentrations of total tau, phospho-tau and amyloid beta (A beta 42) in all individuals. Sixty-three proteins showed significant correlations to either total tau, phospho-tau or A beta 42. Thereafter, individuals were divided based on CSF A beta 42/A beta 40 ratio and Clinical Dementia Rating (CDR) score to determine if early changes in pathology and cognition had an effect on the correlations. We compared the associations of the analysed proteins with CSF markers between groups and found 33 proteins displaying significantly different associations for amyloid-positive individuals and amyloid-negative individuals, as defined by the CSF A beta 42/A beta 40 ratio. No differences in the associations could be seen for individuals divided by CDR score. Conclusions We identified a series of transmembrane proteins, proteins associated with or anchored to the plasma membrane, and proteins involved in or connected to synaptic vesicle transport to be associated with CSF biomarkers of amyloid and tau pathology in AD. Further studies are needed to explore these proteins' role in AD pathophysiology.
|
|
| 7. |
- Remnestål, Julia, et al.
(författare)
-
Association of CSF proteins with tau and amyloid β levels in asymptomatic 70-year-olds.
- 2021
-
Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Increased knowledge of the evolution of molecular changes in neurodegenerative disorders such as Alzheimer's disease (AD) is important for the understanding of disease pathophysiology and also crucial to be able to identify and validate disease biomarkers. While several biological changes that occur early in the disease development have already been recognized, the need for further characterization of the pathophysiological mechanisms behind AD still remains.In this study, we investigated cerebrospinal fluid (CSF) levels of 104 proteins in 307 asymptomatic 70-year-olds from the H70 Gothenburg Birth Cohort Studies using a multiplexed antibody- and bead-based technology.The protein levels were first correlated with the core AD CSF biomarker concentrations of total tau, phospho-tau and amyloid beta (Aβ42) in all individuals. Sixty-three proteins showed significant correlations to either total tau, phospho-tau or Aβ42. Thereafter, individuals were divided based on CSF Aβ42/Aβ40 ratio and Clinical Dementia Rating (CDR) score to determine if early changes in pathology and cognition had an effect on the correlations. We compared the associations of the analysed proteins with CSF markers between groups and found 33 proteins displaying significantly different associations for amyloid-positive individuals and amyloid-negative individuals, as defined by the CSF Aβ42/Aβ40 ratio. No differences in the associations could be seen for individuals divided by CDR score.We identified a series of transmembrane proteins, proteins associated with or anchored to the plasma membrane, and proteins involved in or connected to synaptic vesicle transport to be associated with CSF biomarkers of amyloid and tau pathology in AD. Further studies are needed to explore these proteins' role in AD pathophysiology.
|
|
| 8. |
|
|
| 9. |
- Strömberg, Sara, et al.
(författare)
-
A high-throughput strategy for protein profiling in cell microarrays using automated image analysis
- 2007
-
Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 7:13, s. 2142-2150
-
Tidskriftsartikel (refereegranskat)abstract
- Advances in antibody production render a growing supply of affinity reagents for immunohistochemistry (IHC), and tissue microarray (TMA) technologies facilitate simultaneous analysis of protein expression in a multitude of tissues. However, collecting validated IHC data remains a bottleneck problem, as the standard method is manual microscopical analysis. Here we present a high-throughput strategy combining IHC on a recently developed cell microarray with a novel, automated image-analysis application (TMAx). The software was evaluated on 200 digital images of IHC-stained cell spots, by comparing TMAx annotation with manual annotation performed by seven human experts. A high concordance between automated and manual annotation of staining intensity and fraction of IHC-positive cells was found. in a limited study, we also investigated the possibility to assess the correlation between mRNA and protein levels, by using TMAx output results for relative protein quantification and quantitative real-time PCR for the quantification of corresponding transcript levels. In conclusion, automated analysis of immunohistochemically stained in vitro-cultured cells in a microarray format can be used for high-throughput protein profiling, and extraction of RNA from the same cell lines provides a basis for comparing transcription and protein expression on a global scale.
|
|
| 10. |
|
|
