Document Information

PMID 14597108  (  )
Title Intrathecal synthesis of monocyte chemoattractant protein-1 (MCP-1) in amyotrophic lateral sclerosis: further evidence for microglial activation in neurodegeneration.
Abstract Autopsy studies and animal experiments suggest that microglial inflammation contributes to the pathogenesis of amyotrophic lateral sclerosis (ALS). Monocyte-chemoattractant protein (MCP-1) might play an important role in microglial recruitment. We studied MCP-1 levels in sera and cerebrospinal fluid of 29 ALS patients and compared the results with 11 control patients with tension headache. The MCP-1 level was determined using enzyme-linked immunosorbent assays (ELISA). A significant increase in cerebrospinal fluid MCP-1 level but not serum level was seen in the patients with ALS compared to the control subjects. These results suggest that cerebrospinal fluid MCP-1 activity may be a sensitive marker for neuroinflammation in ALS useful for monitoring treatment trials in ALS. 147, 24105 Kiel, Germany. h.wilms@neurologie.uni-kiel.de

NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.


Targets by SciMiner Summary

HUGO ID Symbol Target Name #Occur ActualStr
10618CCL2chemokine (C-C motif) ligand 263monocyte chemoattractant protein 1 | mcp 1 | MCP-1 |
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))3SOD1 | superoxide dismutase |
6018IL6interleukin 6 (interferon, beta 2)1interleukin 6 |

 

Targets by SciMiner Full list

HUGO ID Symbol Name ActualStr Score FlankingText
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8Monocyte-chemoattractant protein (MCP-1) MCP-1 might play an important role in microglial recruitment
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8We studied MCP-1 levels in sera and cerebrospinal fluid of 29 ALS patients
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8The MCP-1 level was determined using enzyme-linked immunosorbent assays (ELISA) ELISA
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8A significant increase in cerebrospinal fluid MCP-1 level but not serum level was seen in the patients
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8These results suggest that cerebrospinal fluid MCP-1 activity may be a sensitive marker for neuroinflammation in ALS
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD11.4Cu/Zn Cu Zn form of the superoxide dismutase gene (SOD1), SOD1 an animal model of ALS Alexianu et al. 2001
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8Especially monocyte chemoattractant protein-1 (MCP-1) MCP-1 Maghazachi et al. 1994 may be a key trigger for
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8MCP-1 was found immunohistochemically in mature senile plaques and reactive microglia
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8Changes in MCP-1 in living patients with ALS have not been studied however
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8Therefore the present study compares the MCP-1 level in CSF and serum of patients with ALS with
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8MCP-1 levels in serum and CSF samples were quantified by ELISA
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8The Mann_amp_#x2013 Whitney U -test was used to compare MCP-1 levels in CSF and serum in ALS patients with controls
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8relationship between age at time of lumbar puncture and intrathecal MCP-1 levels 3
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8The CSF concentration of MCP-1 was significantly ( p _amp_#x3c 0.001 higher in ALS patients
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8an overlap of values was seen among the ALS group MCP-1 values of only 8 patients of 29 were lower than
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8Furthermore MCP-1 levels in ALS patients (570.5_amp_#xb1;199.9 570.5_amp_#xb1 199.9 pg/ml) pg ml
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8onset of symptoms nor of duration of the disease on MCP-1 levels
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8relationship between age at time of lumbar puncture and intrathecal MCP-1 level in ALS patients ( r =0.045 Fig 1a or
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8This is the first study demonstrating that MCP-1 inflammatory signalling might mediate recruitment of myelomonocytic cells to areas
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8provide in vivo evidence for elevated cerebrospinal fluid levels of MCP-1 in ALS patients providing further evidence for the hypothesis that
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8The higher levels of MCP-1 in the CSF than in paired serum samples in patients
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8activation of astrocytes and microglial cells induces a release of MCP-1 a chemokine produced by both glial cell types Hayashi et
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8Since MCP-1 is a potent activator of macrophage function and specifically attracts
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8Therefore one might speculate that MCP-1 might further increase during the course of ALS
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8Repetitive measurement of MCP-1 may be a useful laboratory marker to follow-up patients participating
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8between clinical impairment/progression impairment progression of the disease and CSF MCP-1 levels a larger sample size may be needed to address
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8In experimental autoimmune encephalomyelitis absence of MCP-1 in mice leads to decreased local macrophage recruitment and antigen-specific
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8note is that bindarit an indazolic derivative able to inhibit MCP-1 is able to ameliorate adjuvant arthritis in rats Guglielmotti et
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8The present data suggest that MCP-1 levels in CSF may be an appropriate surrogate marker in
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8worthwhile to examine the prognostic value of CSF/plasma CSF plasma MCP-1 ratios in ALS patients who are followed longitudinally which should
10618CCL2chemokine (C-C motif) ligand 2MCP-12.8between age at the time of lumbar puncture and intrathecal MCP-1 levels in ALS patients (a) a and control patients (b)
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0monocyte chemoattractant protein mcp 1 might play an important role in microglial recruitment.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0we studied mcp 1 levels in sera and cerebrospinal fluid of 29 als patients and compared the results with 11 control patients with tension headache.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0the mcp 1 level was determined using enzyme linked immunosorbent assays elisa .
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0a significant increase in cerebrospinal fluid mcp 1 level but not serum level was seen in the patients with als compared to the control subjects.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0these results suggest that cerebrospinal fluid mcp 1 activity may be a sensitive marker for neuroinflammation in als useful for monitoring treatment trials in als.
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase1.0glial cells the resident macrophages of the cns are present before the onset of clinical symptoms and prior to significant motor neuron loss in transgenic mice with mutations of the cu/zn form of the superoxide dismutase gene sod1 an animal model of als [ alexianu et al. 2001 ].
6018IL6interleukin 6 (interferon, beta 2)interleukin 61.0ediators released from activated microglia which have harmful effects on neuron survival including peroxynitrite [ beal et al. 1997 and tohgi et al. 1999 ] prostaglandin e 2 [ almer et al. 2002 ] and interleukin 6 [ sekizawa et al. 1998 ] has been demonstrated in the cerebrospinal fluid and spinal cord of als patients for review see [ mcgeer and mcgeer 2002 ] .
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase1.0interestingly minocycline a broad spectrum antibiotic inhibiting microglial activation and proliferation [ tikka et al. 2001 and yrjanheikki et al. 1999 ] is neuroprotective in mutant superoxide dismutase transgenic mouse models of als [ kriz et al. 2002 van den bosch et al. 2002 and zhu et al. 2002 ].
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0especially monocyte chemoattractant protein 1 mcp 1 [ maghazachi et al. 1994 ] may be a key trigger for mediating chemotaxis of monocytes to the injured cns since it is a potent activator of macrophage function [ sozzani et al. 1995 ].
10618CCL2chemokine (C-C motif) ligand 2monocyte chemoattractant protein 11.0especially monocyte chemoattractant protein 1 mcp 1 [ maghazachi et al. 1994 ] may be a key trigger for mediating chemotaxis of monocytes to the injured cns since it is a potent activator of macrophage function [ sozzani et al. 1995 ].
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0mcp 1 was found immunohistochemically in mature senile plaques and reactive microglia in brain tissues of patients suffering from alzheimer's disease [ ishizuka et al. 1997 ] as well as in demyelinating pl
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0changes in mcp 1 in living patients with als have not been studied however its evaluation might aid in understanding the pathogenesis of the disease.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0therefore the present study compares the mcp 1 level in csf and serum of patients with als with that in controls. 2.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0mcp 1 levels in serum and csf samples were quantified by elisa quantikine r_amp_#x26;d systems according to the manufacturer's instructions and read at a wavelength of 450 nm reference wavelength 550 nm wi
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0the mann_amp_#x2013;whitney u test was used to compare mcp 1 levels in csf and serum in als patients with controls.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0regression analysis was used to test for a possible relationship between age at time of lumbar puncture and intrathecal mcp 1 levels. 3.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0the csf concentration of mcp 1 was significantly p _amp_#x3c;0.001 higher in als patients 570.5_amp_#xb1;199.9 pg/ml as compared to controls 285.5_amp_#xb1;81.8 pg/ml .
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0although an overlap of values was seen among the als group mcp 1 values of only 8 patients of 29 were lower than or equal to the highest value in the control group i.e 396.8 pg/ml .
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0furthermore mcp 1 levels in als patients 570.5_amp_#xb1;199.9 pg/ml were substantially higher in the csf p _amp_#x3c;0.001 than in the serum 191.6_amp_#xb1;104.9 pg/ml .
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0by analysis of variance there was no significant influence of age at onset of symptoms nor of duration of the disease on mcp 1 levels.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0regression analysis did not reveal a strong relationship between age at time of lumbar puncture and intrathecal mcp 1 level in als patients r =0.045; fig 1a or control patients r =0 12; fig 1b . 4.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0this is the first study demonstrating that mcp 1 inflammatory signalling might mediate recruitment of myelomonocytic cells to areas of neurodegeneration in als.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0the present findings provide in vivo evidence for elevated cerebrospinal fluid levels of mcp 1 in als patients providing further evidence for the hypothesis that inflammatory processes contribute to neurodegeneration in als.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0the higher levels of mcp 1 in the csf than in paired serum samples in patients with als provide evidence for intrathecal synthesis of this chemokine.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0we hypothesize that degeneration of motor neurons in the lumbar spinal cord with subsequent activation of astrocytes and microglial cells induces a release of mcp 1 a chemokine produced by both glial cell types [ hayashi et al. 1995 ].
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0since mcp 1 is a potent activator of macrophage function and specifically attracts myelomonocytic cells [ calvo et al. 1996 and glabinski et al. 1997 ] it most likely triggers further immigration/activation of m
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0therefore one might speculate that mcp 1 might further increase during the course of als.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0repetitive measurement of mcp 1 may be a useful laboratory marker to follow up patients participating in neuroprotective drug trials.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0due to the lack of correlation between clinical impairment/progression of the disease and csf mcp 1 levels a larger sample size may be needed to address this specific question.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0from a clinical perspective it would be interesting to explore the potential of immunotherapies specifically targeting mcp 1 dependant mechanisms in als.
10618CCL2chemokine (C-C motif) ligand 2monocyte chemoattractant protein 11.0monocyte chemoattractant protein 1 deficiency is protective in a murine stroke model [ hughes et al. 2002 ].
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0in experimental autoimmune encephalomyelitis absence of mcp 1 in mice leads to decreased local macrophage recruitment and antigen specific t helper cell type 1 immune response [ huang et al. 2001 ].
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0of note is that bindarit an indazolic derivative able to inhibit mcp 1 is able to ameliorate adjuvant arthritis in rats [ guglielmotti et al. 2002 ].
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0the present data suggest that mcp 1 levels in csf may be an appropriate surrogate marker in the diagnosis or in treatment of patients with als.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0furthermore it would be worthwhile to examine the prognostic value of csf/plasma mcp 1 ratios in als patients who are followed longitudinally which should be done in further studies.
10618CCL2chemokine (C-C motif) ligand 2mcp 11.0correlation between age at the time of lumbar puncture and intrathecal mcp 1 levels in als patients a and control patients b .