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A cell-permeable peptide system for the treatment of diseases caused by glutamate excitotoxicity

A technology of glutamic acid and cells, applied in the medical field, can solve undiscovered problems

Active Publication Date: 2020-12-18
马尔科费利焦尼 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although JNK is commonly associated with postsynaptic NMDA receptors, its presynaptic role remains largely undiscovered

Method used

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  • A cell-permeable peptide system for the treatment of diseases caused by glutamate excitotoxicity
  • A cell-permeable peptide system for the treatment of diseases caused by glutamate excitotoxicity
  • A cell-permeable peptide system for the treatment of diseases caused by glutamate excitotoxicity

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Experimental program
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Embodiment Construction

[0061] The present invention is based on the demonstration of the presence of JNK isoforms (JNK1, JNK2, JNK3) at the presynaptic level of STX1a. Using this protein interaction as a starting point, two peptides were designed: cell-permeable JGRi1 and JGRi2, which were able to block this JNK2-STX1a interaction and reduce glutamate release induced by stimulation of NMDA receptors.

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Abstract

Peptide system including at least one peptide blocking the presynaptic release of glutamate. The peptide has the sequence SEQ ID NO 5: GRKKRRQRRRPPIEQSIEQEEGLNRS and / or sequence SEQ ID NO 8: GRKKRRQRRRPPMSEYNATQSDYRER for use in treating pathologies associated with glutamate excitotoxicity.

Description

technical field [0001] The present invention relates to the medical field. In more detail, the present invention relates to novel peptide systems capable of blocking NMDA-induced presynaptic release of glutamate. The peptide systems of the invention are useful in the treatment of conditions associated with glutamate excitotoxicity. Background technique [0002] One of the most abundant amino acids in the brain is L-glutamate. Its most important function at the neuronal level is the control of excitatory neurotransmission, which has been described since the 1950s, and its physiological antagonist is gamma-aminobutyric acid (GABA). [0003] L-glutamate is considered a major mediator of excitatory signaling and rapid synaptic transmission in the central nervous system. L-glutamate plays an important role in the development of the central nervous system (CNS), in the formation and elimination of synapses, and in cell migration, differentiation and death. In addition, L-gluta...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K19/00C07K1/04C07K1/16C12N1/21A61K38/16A61P25/28A61P25/16A61P21/00A61P9/10A61P37/02A61P25/18A61P25/22A61P25/06A61P25/00C12R1/19
CPCA61K38/00C07K14/705C07K2319/03A61K38/162A61K38/177A61P9/10A61P21/00A61P21/02A61P25/00A61P25/04A61P25/06A61P25/14A61P25/16A61P25/18A61P25/22A61P25/24A61P25/28A61P29/02A61P37/02A61P43/00Y02A50/30A61K47/6425C07K1/04C07K1/16C12N15/70C07K14/005C07K2319/10C12N2740/16322C12N2800/101
Inventor 马尔科·费利焦尼罗伯特·乔瓦尼·尼斯蒂科
Owner 马尔科费利焦尼
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