Cell-Permeable Peptide Inhibitors of the JNK Signal Transduction Pathway

Abstract

The invention provides cell-permeable peptides that bind to JNK proteins and inhibit JNK-mediated effects in JNK-expressing cells.

1 . A method of inhibiting neuronal cell damage in a subject, comprising administering to the subject prior to identification of said cell damage a composition comprising a peptide selected from the group consisting of the amino acid sequence of SEQ ID NOs: 1-6, 11-16 and 23-26. 
     
     
         2 . The method of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 23. 
     
     
         3 . The method of  claim 1 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 24. 
     
     
         4 . The method of  claim 1 , wherein the subject is a risk for developing a condition characterized by aberrant cell damage. 
     
     
         5 . The method of  claim 4 , wherein said aberrant cell damage is excitotoxic cell death. 
     
     
         6 . The method of  claim 4 , wherein said aberrant cell damage is apoptotic cell death. 
     
     
         7 . The method of  claim 1 , wherein said subject is at risk of developing stroke, amyotrophic lateral sclerosis, epilepsy, multiple sclerosis, Alzheimer's disease, Parkinson's disease, Huntington disease, neurolathyrism, human immunodeficiency virus dementia or autoimmune disease. 
     
     
         8 . The method of  claim 7 , wherein said stroke is ischemic stroke. 
     
     
         9 - 10 . (canceled) 
     
     
         11 . The method of claim  10 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 23. 
     
     
         12 . The method of claim  10 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 24. 
     
     
         13 . The method of claim  10 , wherein said neuronal disorder is selected from the group consisting of stroke, amyotropic lateral sclerosis, epilepsy, multiple sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, neurolathyrism, and human immunodeficiency virus dementia. 
     
     
         14 . A method of treating a neuronal disorder, comprising administering to said mammal a composition comprising a peptide selected from the group consisting of the amino acid sequence of SEQ ID NOs: 1-6, 11-16 and 23-26. 
     
     
         15 . The method of  claim 14 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 23. 
     
     
         16 . The method of  claim 14 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 24. 
     
     
         17 . The method of  claim 14 , wherein said neuronal disorder is selected form the group consisting of stroke, amyotrophic lateral sclerosis, epilepsy, multiple sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, neurolathyrism, and human immunodeficiency virus dementia. 
     
     
         18 . A method of inhibiting neuronal cell death, comprising contacting said cell with a composition comprising a peptide selected form the group consisting of SEQ ID NOs: 1-6, 11-16 and 23-26. 
     
     
         19 . The method of  claim 18 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 23. 
     
     
         20 . The method of  claim 18 , wherein the peptide comprises the amino acid sequence of SEQ ID NO: 24. 
     
     
         21 . The method of  claim 18 , wherein said cell death is excitotoxic cell death. 
     
     
         22 . The method of  claim 18 , wherein said cell death is apoptotic cell death.