Table II. MS-associated proteins.
According to the literature, some of the source proteins have been shown previously to be associated with MS. These could be categorized in regard to the function and tissue localization. IGF, insulin-like growth factor; RR, relapsing-remitting; SPARC, secreted protein acid rich in cysteine; IFN, interferon.
| Entrez ID | Protein | Patients | Association with MS |
|---|---|---|---|
| Apoptosis | |||
| 311 | Annexin A1 | MS1, MS2, MS4, MS7 | Identified as potential new marker of active MS disease (49) |
| 9774 | Bcl-2 associated transcription factor 1 | MS4, MS6 | Antiapoptotic molecule increased in MS cortical neurons (50) |
| 332 | Survivin | MS2 | Heightened expression in activated T cells from MS patients (51) |
| Cytoskeleton | |||
| 60 | Actin | MS1, MS2, MS4, MS5, MS6, MS7, MS8 | Biomarker of axonal and neuronal damage (47) |
| 10376 | α-Tubulin | MS4, MS5, MS6, MS7 | Biomarker of axonal and neuronal damage (47) |
| 2934 | Gelsolin | MS5 | Lower gelsolin concentration in CSF of MS patients, indicating the possible utility for diagnostic purposes (32) |
| 4131 | Microtubule-associated protein 1B (MAP1B) | MS3 | MAP1B is a marker for actively myelinating oligodendrocytes in adult rat brain (52) |
| 3925 | Stathmin 1 | MS4 | Increased stathmin expression in the brains of MS patients (53) |
| Enzymes | |||
| 801 | Calmodulin 1 | MS5 | Calmodulin binds MBP in Ca2+-dependent manner (54) |
| 805 | Calmodulin 2 (phosphorylase kinase) | MS4, MS6 | Involved in migration of γ/δ T cells to the site of lesion in MS (55) |
| 2747 | Glutamate dehydrogenase (GDH) | MS3, MS5, MS3, MS5 | Glutamate excitotoxicity, evoked by altered glutamate homeostasis, was demonstrated in an animal model of MS; GS and GDH are present in oligodendrocytes in normal and non-MS white matter but are absent from active and chronic silent MS lesions, suggesting lasting metabolic impediments (30) |
| 2752 | Glutamine synthetase (GS) | MS1, MS3, MS4, MS5, MS7, MS8 | Glutamate excitotoxicity, evoked by altered glutamate homeostasis, was demonstrated in an animal model of MS; GS and GDH are present in oligodendrocytes in normal and non-MS white matter but are absent from active and chronic silent MS lesions, suggesting lasting metabolic impediments (30) |
| 2597 | Glyceraldehyde-3-phosphate dehydrogenase | MS1, MS3, MS4, MS6, MS7 | Autoantibodies in CSF of patients with MS (31) |
| 51564 | Histone deacetylase 7a | MS6 | Histone deacetylase inhibitors are discussed as a dual therapeutic modality in MS (56) |
| 4696 | NADH dehydrogenase | MS4, MS5 | There is a trend for impaired NADH dehydrogenase activity in association with oxidative damage to mitochondrial DNA in chronic active plaques in MS (57) |
| 113791 | Phosphoinositide 3-kinase (PI3K) | MS1 | Patients with RR-MS display an increase in peripheral Vδ2 γ/δ T cells; they transmigrate across endothelial cells by activation of the PI3K pathway (58) |
| Immune response | |||
| 336 | Early pregnancy factor (EPF) | MS1, MS3, MS4, MS5, MS8 | EPF has a protective effect on EAE in LEW rats (59) |
| 3577 | Interleukin 8 receptor, CXCR1 | MS8 | Treatment with methylprednisolone and mitoxantrone modulates the expression of CXCR1 in blood mononuclear cells (60); CXCR1 is constitutively expressed on oligodendrocytes and up-regulated around active and silent lesions in MS patients (61) |
| 3594 | Interleukin 12 receptor | MS12 | Suggested as a biomarker that can differentiate between relapsing-remitting and secondary progressive MS stages (47) |
| 4282 | Macrophage migration-inhibitory factor | MS4 | A therapeutic target in inflammatory diseases (62) |
| 3119 | MHC class antigen II HLA-DQβ1 | MS2 | HLA-DR and -DQ genes are the strongest genetic risk factors in MS (20, 45) |
| CNS | |||
| 6622 | α-Synuclein | MS4 | Up-regulated in neurons and glia (63) |
| 2670 | GFAP | MS2, MS5, MS6, MS8 | Elevated in CSF of MS patients (27); biomarker of gliosis (47) |
| 4155 | MBP | MS1, MS3, MS6, MS7, MS8 | Anti-MBP antibodies suggested for prediction of development of MS; biomarker of demyelination (47) |
| 4741 | Neurofilament-3, NF-M | MS7, MS8 | Biomarker of axonal and neuronal damage (47); autoantibodies in serum and CSF (64); transgenic MOG-(35–55)-reactive T cells respond to an NF-M epitope in MOG-deficient mice (29) |
| 4747 | Neurofilament light polypeptide, NF-L | MS3, MS6 | Biomarker of axonal and neuronal damage (47); elevated in CSF of MS patients (27); immunization with NF-L induces neurological disease and axonal degeneration in mice (28); autoantibodies in serum and CSF (65) |
| 6285 | S100 calcium-binding protein | MS2 | Raised levels in CSF in RR-MS patients (66) |
| 8404 | SPARC-like protein 1 | MS1, MS2, MS3, MS5 | Present in the CSF of MS patients (67) |
| 3925 | Stathmin 1 | MS4 | Increased expression of stathmin in CNS of MS patients (53) |
| Serum proteins | |||
| 2 | α2-Macroglobulin | MS2, MS8 | Significantly increased fractions of transformed to total α2-macroglobulin in plasma from patients with MS (68, 69) |
| 347 | Apolipoprotein D (apoD) | MS2 | Intrathecal apoD production is increased in MS, CSF apoD traces correlate with disease duration, corticosteroid treatment results in elevated CSF apoD levels (70) |
| 348 | Apolipoprotein E (apoE) | MS4 | ApoE-derived peptides ameliorate clinical disability and inflammatory infiltrates in the spinal cord in EAE (71) |
| 2512 | Ferritin | MS2, MS8 | Elevated ferritin levels in MS patients with chronic progressive active disease (72); elevated levels of ferritin are found in a certain percentage of MS patients (73) |
| 7018 | Transferrin | MS2 | There is evidence for iron dysregulation in the pathogenesis of MS; opposite to the ferritin levels, transferrin levels in patients are in a normal range (72) |
| 7450 | von Willebrand factor | MS7 | CXCR3−/− mice with EAE show more von Willebrand factor-immunoreactive vessels within inflamed spinal cords as compared with CXCR3+/+ mice (74) |
| Others | |||
| 2784 | Guanine nucleotide-binding protein (GNB) | MS4 | Trend to an increased GNB polymorphism in primary chronic progressive MS patients (75) |
| 4600 | Interferon-regulated resistance GTP-binding protein (MX1) | MS3 | Biomarker to measure IFN-β activity in mice following gene-based delivery (76) |
| 10226 | Mannose 6-phosphate receptor (IGF-II) | MS4 | No expression in plaques of MS patients that were characterized by a dense network of astrocytes, suggesting that IGF-II receptors in human brain are not involved in astrogliosis (77) |
| 7157 | p53 tumor suppressor | MS2 | Defects in the ATM-CHK2-p53 pathway in MS patients likely alter the regulation of the immune population of cells in MS and may contribute to the development or progression of the disease (78); increased p53 expression in oligodendrocytes in active MS lesion, feature in oligodendrocyte apoptosis and cell loss (79) |
| 7082 | Tight junction protein ZO-1 | MS4 | Abnormal tight junctions are most frequent in active white matter lesions but persist in inactive lesions of MS patients (80) |