KDI tripeptide of gamma1 laminin protects rat dopaminergic neurons from 6-OHDA induced toxicity.
Our previous studies indicate that the KDI (Lys-Asp-Ile) tripeptide of gamma1 laminin protects central neurons from mechanical trauma and excitotoxicity. At least part of the neuroprotective effect of the KDI tripeptide may be mediated by its inhibitory function on ionotropic glutamate receptors. We studied the protective effect of the KDI tripeptide against 6-hydroxy-dopamine (6-OHDA) induced neurotoxicity in a rat experimental model of Parkinson's disease (PD). We found that a single unilateral injection of the KDI tripeptide into the substantia nigra before an injection of 6-OHDA protected the dopaminergic neurons from the neurotoxicity of 6-OHDA. Compared to rats treated with 6-OHDA alone, the KDI + 6-OHDA-treated substantia nigra was relatively intact with large numbers of dopaminergic neurons present at the injection side. In the rats treated with 6-OHDA alone, no dopaminergic neurons were detected, and the substantia nigra-area at the injection side was filled with blood-containing cavities. Quantification of the rescue effect of the KDI tripeptide indicated that, in animals receiving KDI before 6-OHDA, 33% of tyrosine hydroxylase-positive dopaminergic neurons of the substantia nigra were present as compared to the contralateral non-injected side. In animals receiving 6-OHDA alone, only 1.4% of the tyrosine hydroxylase expressing dopaminergic neurons could be verified. If this much protection were achieved in humans, it would be sufficient to diminish or greatly alleviate the clinical symptoms of PD. We propose that the KDI tripeptide or its derivatives might offer a neuroprotective biological alternative for treatment of PD.
Väänänen
Antti J
AJ
The Brain Laboratory, Department of Biological and Environmental Sciences (Physiology), University of Helsinki, Finland.
Rauhala
Pekka
P
Tuominen
Raimo K
RK
Liesi
Päivi
P
D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D007797:Laminin / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D016627:Oxidopamine / Q000037:antagonists & inhibitors / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016896:Treatment Outcome; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism
D007797:Laminin; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010446:Peptide Fragments; D017470:Receptors, Glutamate; C089141:laminin gamma 1; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine