)| PMID |
15571972 ( ) |
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| Title | Clinical potential of minocycline for neurodegenerative disorders. |
| Abstract | Minocycline, an antibiotic of the tetracycline family, has been shown to display neurorestorative or neuroprotective properties in various models of neurodegenerative diseases. In particular, it has been shown to delay motor alterations, inflammation and apoptosis in models of Huntington's disease, amyotrophic lateral sclerosis and Parkinson's disease. Despite controversies about its efficacy, the relative safety and tolerability of minocycline have led to the launching of various clinical trials. The present review summarizes the available data supporting the clinical testing of minocycline for these neurodegenerative disorders. In addition, we extend our discussion to the potential applications of minocycline for combining this treatment with cellular and molecular therapy. Belgium. David.Blum@ulb.ac.be |
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 |
|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 5 | SOD1 | SOD | |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | 4 | Bcl-2 | bcl 2 | |
| 4851 | HTT | huntingtin | 4 | huntingtin | |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | 3 | apoptosis inducing factor | AIF | |
| 19986 | CYCS | cytochrome c, somatic | 2 | cytochrome c | |
| 21528 | DIABLO | diablo homolog (Drosophila) | 2 | Smac | |
| 6563 | LGALS3 | lectin, galactoside-binding, soluble, 3 | 2 | mac 2 | MAC-2 | |
| 26515 | COQ10A | coenzyme Q10 homolog A (S. cerevisiae) | 2 | Q10 | |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | 1 | amyloid | |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | 1 | caspase 1 | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 1 | nitric oxide synthase | |
| 6149 | ITGAM | integrin, alpha M (complement component 3 receptor 3 subunit) | 1 | CD11b | |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | 1 | caspase 3 | |
| 10935 | SLC18A2 | solute carrier family 18 (vesicular monoamine), member 2 | 1 | VMAT2 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 21528 | DIABLO | diablo homolog (Drosophila) | Smac | 1.3 | see Blum et al. 2001 such as cytochrome c Smac/Diablo Smac Diablo or Apoptosis Inducing Factor (AIF; AIF Wang et al. |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | AIF | 0.6 | cytochrome c Smac/Diablo Smac Diablo or Apoptosis Inducing Factor (AIF; AIF Wang et al. 2003a |
| 26515 | COQ10A | coenzyme Q10 homolog A (S. cerevisiae) | Q10 | 0.9 | genetic mouse models such as suberoylanilide hydroxamic acid or coenzyme Q10 may or not modulate the presence of aggregates ( Hockly |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | work suggesting that tetracyclines can inhibit the formation of _amp_#x3b2 -amyloid aggregates and are able to disassemble preformed fibrils ( Forloni |
| 10935 | SLC18A2 | solute carrier family 18 (vesicular monoamine), member 2 | VMAT2 | 1.3 | to compromise the activity of the vesicular monoamine transporter (VMAT2; VMAT2 Yang et al. 2003 that could promote chemical toxicity of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.0 | therapeutic efficacy of the antibiotic has been tested in the SOD G93A (10_amp_#x2013;50 10_amp_#x2013 50 mg/kg mg kg i.p Van Den |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.0 | al. 2002 and Zhu et al. 2002 and in the SOD G37R (1 1 g/kg g kg in diet Kriz et |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.0 | against the neurotoxicity of CSF coming from patients carrying the SOD D90A mutation ( Tikka et al. 2002 |
| 6149 | ITGAM | integrin, alpha M (complement component 3 receptor 3 subunit) | CD11b | 1.0 | proliferation activation of resting microglial cells as revealed by CD11b/OX-42, CD11b OX-42 MAC-2 or isolectine-B4 staining ( Dommergues et al. 2003 |
| 6563 | LGALS3 | lectin, galactoside-binding, soluble, 3 | MAC-2 | 0.2 | of resting microglial cells as revealed by CD11b/OX-42, CD11b OX-42 MAC-2 or isolectine-B4 staining ( Dommergues et al. 2003 _amp_#x2014 45 |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | AIF | 0.6 | the cytosolic release of apoptogenic factors such as cytochrome c AIF or Smac/Diablo Smac Diablo mediating caspase-dependent and -independent cell death |
| 21528 | DIABLO | diablo homolog (Drosophila) | Smac | 1.3 | of apoptogenic factors such as cytochrome c AIF or Smac/Diablo Smac Diablo mediating caspase-dependent and -independent cell death ( Matsuki et |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 2.1 | been recently shown to up-regulate expression of the anti-apoptotic protein Bcl-2 ( Wang et al. 2004 |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 2.1 | thus the activation_amp_#x2014 of Bid a pro-apoptotic protein of the Bcl-2 family ( Wang et al. 2003a _amp_#x2014 10 mg/kg mg |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.0 | supplements has been shown to be very effective in the SOD1 G37R mouse model of ALS with a major increase of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 1.0 | sole therapy significantly delayed disease onset and increased survival of SOD1 G93A mice ( Zhang et al. 2003b as compared to |
| 26515 | COQ10A | coenzyme Q10 homolog A (S. cerevisiae) | Q10 | 0.9 | communication reported the potential interest to combine minocycline and coenzyme Q10 in the R6/2 R6 2 HD model ( Carreras et |
| 4851 | HTT | huntingtin | huntingtin | 1.0 | recent studies have reported that a daily treatment with minocycline 5_amp_#x2013;10 mg/kg i.p. slows progression and delays mortality of mice carrying the exon 1 of mutated huntingtin with 144 cag repeats when administrated from 8.5 weeks of age carreras et al. 2003 chen et al. 2000 wang et al. 2003b and wang et al. 2003a . |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | apoptosis inducing factor | 1.0 | ompanied by a decrease in the level of interleukin 1_amp_#x3b2; and in the cytosolic release of apoptogenic mitochondrial factors for a review see blum et al. 2001 such as cytochrome c smac/diablo or apoptosis inducing factor aif; wang et al. 2003a . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | ts beneficial effect was accompanied by a decrease in the level of interleukin 1_amp_#x3b2; and in the cytosolic release of apoptogenic mitochondrial factors for a review see blum et al. 2001 such as cytochrome c smac/diablo or apoptosis inducing factor aif; wang et al. 2003a . |
| 4851 | HTT | huntingtin | huntingtin | 1.0 | in vitro minocycline 5_amp_#x2013;100 _amp_#x3bc;m inhibits cell death and apoptosis induced by either mutated huntingtin or other neurotoxic stimulations promoting caspase activation blum et al. unpublished observations; wang et al. 2003a . |
| 4851 | HTT | huntingtin | huntingtin | 1.0 | 2003 using a slice culture model of hd clearly demonstrated that 30 _amp_#x3bc;m minocycline inhibit huntingtin aggregation up to tenfold. |
| 4851 | HTT | huntingtin | huntingtin | 1.0 | however this is inconsistent with other recent in vitro data showing that 50 _amp_#x3bc;m minocycline fails to inhibit aggregation in cells overexpressing mutated huntingtin apostol et al. 2003 . |
| 6563 | LGALS3 | lectin, galactoside-binding, soluble, 3 | mac 2 | 1.0 | morphologically minocycline reduces the proliferation/activation of resting microglial cells as revealed by cd11b/ox 42 mac 2 or isolectine b4 staining dommergues et al. 2003 _amp_#x2014;45 mg/kg i.p.; he et al. 2001 _amp_#x2014;45 mg/kg i.p.; kriz et al. 2002 _amp_#x2014;1 g/kg p.o.; tikka and koistinaho 2001 and tikka et |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | accordingly several studies showed that minocycline reduces the expression of inducible nitric oxide synthase and subsequent nitric oxide production as well as caspase 1 activity/expression and thereby prevents the formation of interleukin 1_amp_#x3b2; amin et al. 1996 ; chen et al. 2000 _amp_#x2014;5 mg/kg/d i.p.; du et al. 2001 _amp_#x2014;60 to 120 mg/kg p.o.; yrj |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | accordingly several studies showed that minocycline reduces the expression of inducible nitric oxide synthase and subsequent nitric oxide production as well as caspase 1 activity/expression and thereby prevents the formation of interleukin 1_amp_#x3b2; amin et al. 1996 ; chen et al. 2000 _amp_#x2014;5 mg/kg/ |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | the mitochondrial level to rescue the collapse of transmembrane potential and the alterations of permeability transition which are responsible for the cytosolic release of apoptogenic factors such as cytochrome c aif or smac/diablo mediating caspase dependent and independent cell death matsuki et al. 2003 and wang et al. 2003b _amp_#x2014;5 mg/kg i.p.; zhu et al. 2002 _amp_#x2014;22.5 to 45 mg/kg i.p. . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | additionally minocycline has been recently shown to up regulate expression of the anti apoptotic protein bcl 2 wang et al. 2004 . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | minocycline can also reduce the cleavage_amp_#x2014;and thus the activation_amp_#x2014;of bid a pro apoptotic protein of the bcl 2 family wang et al. 2003a _amp_#x2014;10 mg/kg i.p. . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | this was accompanied by a substantial reduction of caspase 3 activity inflammation and gliosis kriz et al. 2003 . |