CA2273622C - Inhibition de la signalisation induite par le recepteur nmda dans le but de reduire les lesions neuronales - Google Patents
Inhibition de la signalisation induite par le recepteur nmda dans le but de reduire les lesions neuronales Download PDFInfo
- Publication number
- CA2273622C CA2273622C CA2273622A CA2273622A CA2273622C CA 2273622 C CA2273622 C CA 2273622C CA 2273622 A CA2273622 A CA 2273622A CA 2273622 A CA2273622 A CA 2273622A CA 2273622 C CA2273622 C CA 2273622C
- Authority
- CA
- Canada
- Prior art keywords
- peptide
- tsxv
- motif
- containing peptide
- excitotoxicity
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 title abstract description 65
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 title abstract description 64
- 230000011664 signaling Effects 0.000 title description 11
- 230000005764 inhibitory process Effects 0.000 title description 4
- 230000003961 neuronal insult Effects 0.000 title description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 65
- 230000003492 excitotoxic effect Effects 0.000 claims abstract description 24
- 230000000254 damaging effect Effects 0.000 claims abstract description 22
- 231100000063 excitotoxicity Toxicity 0.000 claims abstract description 21
- 241000124008 Mammalia Species 0.000 claims abstract description 20
- 208000014674 injury Diseases 0.000 claims abstract description 17
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 14
- 238000004519 manufacturing process Methods 0.000 claims abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 208000006011 Stroke Diseases 0.000 claims abstract description 12
- 210000004556 brain Anatomy 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 9
- 210000000278 spinal cord Anatomy 0.000 claims abstract description 7
- 230000008736 traumatic injury Effects 0.000 claims abstract description 6
- 208000028867 ischemia Diseases 0.000 claims description 11
- 230000010412 perfusion Effects 0.000 claims description 9
- 201000006474 Brain Ischemia Diseases 0.000 claims description 7
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 7
- 206010008118 cerebral infarction Diseases 0.000 claims description 7
- 208000007536 Thrombosis Diseases 0.000 claims description 4
- 206010047163 Vasospasm Diseases 0.000 claims description 4
- 230000003073 embolic effect Effects 0.000 claims description 4
- 230000001575 pathological effect Effects 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 13
- 239000008280 blood Substances 0.000 claims 3
- 210000004369 blood Anatomy 0.000 claims 3
- 102000047174 Disks Large Homolog 4 Human genes 0.000 abstract description 62
- 108700019745 Disks Large Homolog 4 Proteins 0.000 abstract description 61
- 210000002569 neuron Anatomy 0.000 abstract description 32
- 238000000034 method Methods 0.000 abstract description 21
- 230000006378 damage Effects 0.000 abstract description 18
- 208000027418 Wounds and injury Diseases 0.000 abstract description 11
- 101000941893 Felis catus Leucine-rich repeat and calponin homology domain-containing protein 1 Proteins 0.000 abstract description 9
- 230000008569 process Effects 0.000 abstract description 6
- 230000000302 ischemic effect Effects 0.000 abstract description 5
- 238000011282 treatment Methods 0.000 abstract description 5
- 208000037906 ischaemic injury Diseases 0.000 abstract description 4
- 230000002427 irreversible effect Effects 0.000 abstract description 2
- 101150069842 dlg4 gene Proteins 0.000 abstract 1
- 102000004196 processed proteins & peptides Human genes 0.000 abstract 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 43
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical class O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 43
- 231100000419 toxicity Toxicity 0.000 description 23
- 230000001988 toxicity Effects 0.000 description 23
- 230000000694 effects Effects 0.000 description 20
- 230000000692 anti-sense effect Effects 0.000 description 19
- 230000004913 activation Effects 0.000 description 15
- 238000001994 activation Methods 0.000 description 15
- 238000011068 loading method Methods 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 14
- 230000007812 deficiency Effects 0.000 description 14
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 14
- 102000006538 Nitric Oxide Synthase Type I Human genes 0.000 description 11
- 108010008858 Nitric Oxide Synthase Type I Proteins 0.000 description 11
- 238000002474 experimental method Methods 0.000 description 11
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 108091006146 Channels Proteins 0.000 description 8
- 230000002950 deficient Effects 0.000 description 8
- 230000004941 influx Effects 0.000 description 8
- DLBFLQKQABVKGT-UHFFFAOYSA-L lucifer yellow dye Chemical compound [Li+].[Li+].[O-]S(=O)(=O)C1=CC(C(N(C(=O)NN)C2=O)=O)=C3C2=CC(S([O-])(=O)=O)=CC3=C1N DLBFLQKQABVKGT-UHFFFAOYSA-L 0.000 description 8
- 230000037361 pathway Effects 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 102100024117 Disks large homolog 2 Human genes 0.000 description 7
- 101710185758 Disks large homolog 2 Proteins 0.000 description 7
- 101500027983 Rattus norvegicus Octadecaneuropeptide Proteins 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000003119 immunoblot Methods 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 5
- 102000003678 AMPA Receptors Human genes 0.000 description 5
- 108090000078 AMPA Receptors Proteins 0.000 description 5
- 108020004202 Guanylate Kinase Proteins 0.000 description 5
- 206010029350 Neurotoxicity Diseases 0.000 description 5
- 238000000692 Student's t-test Methods 0.000 description 5
- 206010044221 Toxic encephalopathy Diseases 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- QLTXKCWMEZIHBJ-PJGJYSAQSA-N dizocilpine maleate Chemical compound OC(=O)\C=C/C(O)=O.C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 QLTXKCWMEZIHBJ-PJGJYSAQSA-N 0.000 description 5
- 102000006638 guanylate kinase Human genes 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 230000001537 neural effect Effects 0.000 description 5
- 231100000189 neurotoxic Toxicity 0.000 description 5
- 230000002887 neurotoxic effect Effects 0.000 description 5
- 238000001543 one-way ANOVA Methods 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 4
- 102100022263 Disks large homolog 3 Human genes 0.000 description 4
- 101710185762 Disks large homolog 3 Proteins 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 239000007995 HEPES buffer Substances 0.000 description 4
- VLSMHEGGTFMBBZ-OOZYFLPDSA-M Kainate Chemical compound CC(=C)[C@H]1C[NH2+][C@H](C([O-])=O)[C@H]1CC([O-])=O VLSMHEGGTFMBBZ-OOZYFLPDSA-M 0.000 description 4
- 102000000079 Kainic Acid Receptors Human genes 0.000 description 4
- 108010069902 Kainic Acid Receptors Proteins 0.000 description 4
- KCWZGJVSDFYRIX-YFKPBYRVSA-N N(gamma)-nitro-L-arginine methyl ester Chemical compound COC(=O)[C@@H](N)CCCN=C(N)N[N+]([O-])=O KCWZGJVSDFYRIX-YFKPBYRVSA-N 0.000 description 4
- 108020001305 NR1 subfamily Proteins 0.000 description 4
- 102000034570 NR1 subfamily Human genes 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 4
- 238000000540 analysis of variance Methods 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Chemical compound [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 4
- 210000003618 cortical neuron Anatomy 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 231100000228 neurotoxicity Toxicity 0.000 description 4
- 230000007135 neurotoxicity Effects 0.000 description 4
- 229960000715 nimodipine Drugs 0.000 description 4
- 239000002243 precursor Substances 0.000 description 4
- 208000020431 spinal cord injury Diseases 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 238000012353 t test Methods 0.000 description 4
- 230000001960 triggered effect Effects 0.000 description 4
- RPXVIAFEQBNEAX-UHFFFAOYSA-N 6-Cyano-7-nitroquinoxaline-2,3-dione Chemical compound N1C(=O)C(=O)NC2=C1C=C([N+](=O)[O-])C(C#N)=C2 RPXVIAFEQBNEAX-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 210000004958 brain cell Anatomy 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 230000009460 calcium influx Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 230000002461 excitatory amino acid Effects 0.000 description 3
- 239000003257 excitatory amino acid Substances 0.000 description 3
- 231100000318 excitotoxic Toxicity 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000016273 neuron death Effects 0.000 description 3
- 230000007996 neuronal plasticity Effects 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 3
- 230000006916 protein interaction Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000000946 synaptic effect Effects 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 108020004491 Antisense DNA Proteins 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- WRODMZBHNNPRLN-SRVKXCTJSA-N Lys-Leu-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O WRODMZBHNNPRLN-SRVKXCTJSA-N 0.000 description 2
- 101000902097 Mus musculus Disks large homolog 4 Proteins 0.000 description 2
- 102000002247 NADPH Dehydrogenase Human genes 0.000 description 2
- 108010014870 NADPH Dehydrogenase Proteins 0.000 description 2
- 102000038100 NR2 subfamily Human genes 0.000 description 2
- 108020002076 NR2 subfamily Proteins 0.000 description 2
- XOWVFANEOZMPKG-REOHCLBHSA-N S-nitroso-L-cysteine Chemical compound OC(=O)[C@@H](N)CSN=O XOWVFANEOZMPKG-REOHCLBHSA-N 0.000 description 2
- DJACUBDEDBZKLQ-KBIXCLLPSA-N Ser-Ile-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O DJACUBDEDBZKLQ-KBIXCLLPSA-N 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- VLSMHEGGTFMBBZ-UHFFFAOYSA-N alpha-Kainic acid Natural products CC(=C)C1CNC(C(O)=O)C1CC(O)=O VLSMHEGGTFMBBZ-UHFFFAOYSA-N 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003816 antisense DNA Substances 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 230000001201 calcium accumulation Effects 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000010217 densitometric analysis Methods 0.000 description 2
- 238000001739 density measurement Methods 0.000 description 2
- 238000000586 desensitisation Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 230000000763 evoking effect Effects 0.000 description 2
- 238000002073 fluorescence micrograph Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- VLSMHEGGTFMBBZ-OOZYFLPDSA-N kainic acid Chemical compound CC(=C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VLSMHEGGTFMBBZ-OOZYFLPDSA-N 0.000 description 2
- 229950006874 kainic acid Drugs 0.000 description 2
- 230000013016 learning Effects 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000003094 perturbing effect Effects 0.000 description 2
- 150000004713 phosphodiesters Chemical class 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 description 2
- CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 2
- 229950010357 tetrodotoxin Drugs 0.000 description 2
- CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 230000000472 traumatic effect Effects 0.000 description 2
- ZFLWDHHVRRZMEI-ZDUSSCGKSA-N (4S)-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydropyridine-3-carboxylic acid methyl ester Chemical compound COC(=O)C1=C(C)NC(C)=C([N+]([O-])=O)[C@H]1C1=CC=CC=C1C(F)(F)F ZFLWDHHVRRZMEI-ZDUSSCGKSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 239000000774 AMPA receptor agonist Substances 0.000 description 1
- UEFODXNXUAVPTC-VEVYYDQMSA-N Asp-Thr-Met Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O UEFODXNXUAVPTC-VEVYYDQMSA-N 0.000 description 1
- 239000012583 B-27 Supplement Substances 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- WZJLBUPPZRZNTO-CIUDSAMLSA-N Cys-Ser-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CS)N WZJLBUPPZRZNTO-CIUDSAMLSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- RBXSZQRSEGYDFG-GUBZILKMSA-N Glu-Lys-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O RBXSZQRSEGYDFG-GUBZILKMSA-N 0.000 description 1
- IDEODOAVGCMUQV-GUBZILKMSA-N Glu-Ser-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O IDEODOAVGCMUQV-GUBZILKMSA-N 0.000 description 1
- 102100022630 Glutamate receptor ionotropic, NMDA 2B Human genes 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 206010058558 Hypoperfusion Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 102100022397 Nitric oxide synthase, brain Human genes 0.000 description 1
- 101710111444 Nitric oxide synthase, brain Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000000470 PDZ domains Human genes 0.000 description 1
- 108050008994 PDZ domains Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010038912 Retinoid X Receptors Proteins 0.000 description 1
- 102100027720 SH2 domain-containing protein 1A Human genes 0.000 description 1
- 102100027732 Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 Human genes 0.000 description 1
- 101710184528 Scaffolding protein Proteins 0.000 description 1
- SWSRFJZZMNLMLY-ZKWXMUAHSA-N Ser-Asp-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O SWSRFJZZMNLMLY-ZKWXMUAHSA-N 0.000 description 1
- 108010045517 Serum Amyloid P-Component Proteins 0.000 description 1
- ZUUDNCOCILSYAM-KKHAAJSZSA-N Thr-Asp-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O ZUUDNCOCILSYAM-KKHAAJSZSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003194 amino acid receptor blocking agent Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000003185 calcium uptake Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 210000001787 dendrite Anatomy 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- XEYBHCRIKKKOSS-UHFFFAOYSA-N disodium;azanylidyneoxidanium;iron(2+);pentacyanide Chemical compound [Na+].[Na+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].[O+]#N XEYBHCRIKKKOSS-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000000668 effect on calcium Effects 0.000 description 1
- 230000007831 electrophysiology Effects 0.000 description 1
- 238000002001 electrophysiology Methods 0.000 description 1
- 230000009483 enzymatic pathway Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 230000035611 feeding Effects 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 230000009097 homeostatic mechanism Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000003126 immunogold labeling Methods 0.000 description 1
- 230000003116 impacting effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000002909 kainic acid receptor agonist Substances 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000004130 lipolysis Effects 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 108010056582 methionylglutamic acid Proteins 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000007472 neurodevelopment Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000003955 neuronal function Effects 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 230000005064 nitric oxide mediated signal transduction Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000002135 phase contrast microscopy Methods 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000004850 protein–protein interaction Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 108010069117 seryl-lysyl-aspartic acid Proteins 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940083618 sodium nitroprusside Drugs 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 231100000747 viability assay Toxicity 0.000 description 1
- 238000003026 viability measurement method Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Marine Sciences & Fisheries (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2273622A CA2273622C (fr) | 1999-06-02 | 1999-06-02 | Inhibition de la signalisation induite par le recepteur nmda dans le but de reduire les lesions neuronales |
| US10/208,374 US7595297B2 (en) | 1999-06-02 | 2002-07-30 | Method of reducing injury to mammalian cells |
| US10/930,192 US7510824B2 (en) | 1999-06-02 | 2004-08-31 | Method of screening peptides useful in treating traumatic injury to the brain or spinal cord |
| US11/894,818 US7846897B2 (en) | 1999-06-02 | 2007-08-20 | Agents for reducing injury to mammalian cells |
| US12/392,988 US8071548B2 (en) | 1999-06-02 | 2009-02-25 | Method of reducing injury to mammalian cells |
| US12/557,884 US8648043B2 (en) | 1999-06-02 | 2009-09-11 | Method of reducing injury to mammalian cells |
| US13/286,071 US20120302504A1 (en) | 1999-06-02 | 2011-10-31 | Method Of Reducing Injury To Mammalian Cells |
| US14/279,243 US20150190459A1 (en) | 1999-06-02 | 2014-05-15 | Method Of Reducing Injury To Mammalian Cells |
| US15/292,062 US20170239316A1 (en) | 1999-06-02 | 2016-10-12 | Method Of Reducing Injury To Mammalian Cells |
| US15/956,563 US20180369319A1 (en) | 1999-06-02 | 2018-04-18 | Method of Reducing Injury to Mammalian Cells |
| US16/578,318 US20200222492A1 (en) | 1999-06-02 | 2019-09-21 | Method of Reducing Injury to Mammalian Cells |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2273622A CA2273622C (fr) | 1999-06-02 | 1999-06-02 | Inhibition de la signalisation induite par le recepteur nmda dans le but de reduire les lesions neuronales |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2273622A1 CA2273622A1 (fr) | 2000-12-02 |
| CA2273622C true CA2273622C (fr) | 2012-03-20 |
Family
ID=30774266
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2273622A Expired - Lifetime CA2273622C (fr) | 1999-06-02 | 1999-06-02 | Inhibition de la signalisation induite par le recepteur nmda dans le but de reduire les lesions neuronales |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2273622C (fr) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6942981B1 (en) | 1999-05-14 | 2005-09-13 | Arbor Vita Corporation | Method of determining interactions with PDZ-domain polypeptides |
| AU5011200A (en) * | 1999-05-14 | 2000-12-05 | Arbor Vita Corporation | Molecular interactions in hematopoietic cells |
| US7595297B2 (en) | 1999-06-02 | 2009-09-29 | Michael Tymianski | Method of reducing injury to mammalian cells |
| US7510824B2 (en) | 1999-06-02 | 2009-03-31 | Nono Inc. | Method of screening peptides useful in treating traumatic injury to the brain or spinal cord |
| WO2001087285A2 (fr) * | 2000-05-12 | 2001-11-22 | The Johns Hopkins University | Inhibition de l'interaction de l'antisens psd93 et psd95 avec des recepteurs de nnos et nmda |
| US20020045590A1 (en) | 2000-10-23 | 2002-04-18 | Yuanxiang Tao | Inhibition of interaction of PSD93 and PSD95 with nNOS and NMDA receptors |
| CA2505479A1 (fr) * | 2002-11-14 | 2004-06-03 | Arbor Vita Corporation | Interactions moleculaires dans des neurones |
-
1999
- 1999-06-02 CA CA2273622A patent/CA2273622C/fr not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| CA2273622A1 (fr) | 2000-12-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8648043B2 (en) | Method of reducing injury to mammalian cells | |
| Mandela et al. | The norepinephrine transporter and its regulation | |
| Guttmann et al. | Specific proteolysis of the NR2 subunit at multiple sites by calpain | |
| Shirao et al. | Clustering and anchoring mechanisms of molecular constituents of postsynaptic scaffolds in dendritic spines | |
| Rammes et al. | Myeloid-related protein (MRP) 8 and MRP14, calcium-binding proteins of the S100 family, are secreted by activated monocytes via a novel, tubulin-dependent pathway | |
| Kumaran et al. | Lamin A/C speckles mediate spatial organization of splicing factor compartments and RNA polymerase II transcription | |
| Dreyer et al. | Nitric oxide synthase (NOS)-interacting protein interacts with neuronal NOS and regulates its distribution and activity | |
| Zagon et al. | Zeta (ξ), a growth-related opioid receptor in developing rat cerebellum: identification and characterization | |
| JP2008500266A (ja) | Ampa受容体エンドサイトーシスの阻害剤を用いた神経細胞反応のモジュレート方法 | |
| Bray et al. | A role for the human sperm glycine receptor/Cl− channel in the acrosome reaction initiated by recombinant ZP3 | |
| De Camilli et al. | Synapses | |
| Hannan et al. | Structural compartments within neurons: developmentally regulated organization of microfilament isoform mRNA and protein | |
| JP6253596B2 (ja) | アシル補酵素a:リゾカルジオリピン・アシル基転移酵素1(alcat1)の発現、機能または活性の阻害物質を同定する方法 | |
| US8268795B2 (en) | Emergence of a R-type CA2+ channel (CAV 2.3) contributes to cerebral artery constriction following subarachnoid hemorrhage | |
| Bredt | Targeting nitric oxide to its targets | |
| JP2022505101A (ja) | Nmda受容体媒介毒性を調節するための新規の方法 | |
| JP2015514966A5 (fr) | ||
| Yuen et al. | Postsynaptic density-95 (PSD-95) and calcineurin control the sensitivity of N-methyl-D-aspartate receptors to calpain cleavage in cortical neurons | |
| Lin et al. | The carboxyl terminus of the prolactin-releasing peptide receptor interacts with PDZ domain proteins involved in α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor clustering | |
| Niewenhuis et al. | Calmodulin inhibitors protect against cadmium-induced testicular damage in mice | |
| Zhu et al. | Activation of the NRF2 signaling pathway mitigates arthrofibrosis by suppressing myofibroblast ferroptosis through oxidative stress regulation | |
| Gao et al. | Angiopoietin-like protein 3 regulates the motility and permeability of podocytes by altering nephrin expression in vitro | |
| AU2012272550B2 (en) | Prevention and treatment of acute inflammatory conditions | |
| US7915255B2 (en) | Metabolism-modulating agents and uses therefor | |
| WO2011104309A1 (fr) | Composés pour le traitement de l'inflammation et de la neutropénie |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20190603 |