Is the soluble KDI domain of γ1 laminin a regeneration factor for the mammalian central nervous system?

Liebkind, Ron; Laatikainen, Timo; Liesi, Päivi

doi:10.1002/jnr.10692

Cited by 18 publications

(16 citation statements)

References 36 publications

(66 reference statements)

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“…The A chain pentapeptide sequence IKVAV of laminin has been shown to promote neurite outgrowth (Jucker et al, 1991). The mechanism behind the phenomena may be the existence of the KDI domain in laminin, which has been indicated to neutralize both glial-derived inhibitory signals and inhibitory molecules released from the myelin of the adult CNS (Liebkind et al, 2003). The present study, which has confirmed the critical role of laminin during axon regeneration in the CNS, is nevertheless a study in vivo and this should be an advanced step compared to the previous study.…”

Section: Discussionmentioning

confidence: 98%

The repair of brain lesion by implantation of hyaluronic acid hydrogels modified with laminin

Hou

Tian

et al. 2005

Journal of Neuroscience Methods

198

163

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Section: Discussionmentioning

confidence: 98%

The repair of brain lesion by implantation of hyaluronic acid hydrogels modified with laminin

Hou

Tian

et al. 2005

Journal of Neuroscience Methods

198

163

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“…12 The studies on rats showed no significant side effects. 13 So far, preclinical and clinical researches on glutamate blockers have been focused on stroke and chronic neurological disorders, hence data about their efficiency in SCI are scarce.…”

mentioning

confidence: 94%

A review of published reports on neuroprotection in spinal cord injury

et al. 2009

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Study design: Literature review. Objectives: To review the main published current neuroprotection research trends and results in spinal cord injury (SCI). Setting: This paper is the result of a collaboration between a group of European scientists. Methods: Recent studies, especially in genetic, immune, histochemical and bio (nano)-technological fields, have provided new insight into the cellular and molecular mechanisms occurring within the central nervous system (NS), including SCIs. As a consequence, a new spectrum of therapies aiming to antagonize the 'secondary injury' pathways (that is, to provide neuroprotection) and also to repair such classically irreparable structures is emerging. We reviewed the most significant published works related to such novel, but not yet entirely validated, clinical practice therapies. Results: There have been identified many molecules, primarily expressed by heterogenous glial and neural subpopulations of cells, which are directly or indirectly critical for tissue damaging/sparing/ re-growth inhibiting, angiogenesis and neural plasticity, and also various substances/energy vectors with regenerative properties, such as MAG (myelin-associated glycoprotein), Omgp (oligodendrocyte myelin glycoprotein), KDI (synthetic: Lysine-Asparagine-Isoleucine 'g-1 of Laminin Kainat Domain'), Nogo (Neurite outgrowth inhibitor), NgR (Nogo protein Receptor), the Rho signaling pathway (superfamily of 'Rho-dopsin geneFincluding neurotransmitterFreceptors'), EphA4 (Ephrine), GFAP (Glial Fibrillary Acidic Protein), different subtypes of serotonergic and glutamatergic receptors, antigens, antibodies, immune modulators, adhesion molecules, scavengers, neurotrophic factors, enzymes, hormones, collagen scar inhibitors, remyelinating agents and neurogenetic/plasticity inducers, all aiming to preserve/re-establish the morphology and functional connections across the lesion site. Accordingly, modern research and experimental SCI therapies focus on several intricate, rather overlapping, therapeutic objectives and means, such as neuroprotective, neurotrophic, neurorestorative, neuroreparative, neuroregenerative, neuro(re)constructive and neurogenetic interventions. Conclusion: The first three of these therapeutical directions are generically assimilated as neuroprotective, and are synthetically presented and commented in this paper in an attempt to conceptually systematize them; thus, the aim of this article is, by emphasizing the state-of-the art in the domain, to optimize theoretical support in selecting the most effective pharmacological and physical interventions for preventing, as much as possible, paralysis, and for maximizing recovery chances after SCI.

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“…One of the ways that the KDI tripeptide promotes regeneration and protects central neurons from death may be related to its recently shown ability to inhibit ionotropic glutamate receptors (Möykkynen et al,2005). However, γ1 laminin and its KDI domain do have additional neurotrophic functions, as evidenced by their involvement in neurite outgrowth (Liesi et al,1989,2001a,b; Liebkind et al,2003), neuronal migration (Liesi,1985a,1995), and axon guidance during early CNS development (Liesi and Silver,1988; Matsuzawa et al,1998; Wiksten et al,2003). In addition, the neurite outgrowth domain of γ1 laminin has been shown to promote differentiation of immature neurons (Matsuzawa et al,1996), and to modulate electrical activity of rat cerebellar neurons via a G‐protein coupled mechanism (Liesi et al,2001a), effects that further elucidate its ability to act in a neuroprotective manner.…”

mentioning

confidence: 99%

KDI tripeptide of γ1 laminin protects rat dopaminergic neurons from 6‐OHDA induced toxicity

Väänänen

Rauhala

Tuominen

et al. 2006

J of Neuroscience Research

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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.

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Is the soluble KDI domain of γ1 laminin a regeneration factor for the mammalian central nervous system?

Cited by 18 publications

References 36 publications

The repair of brain lesion by implantation of hyaluronic acid hydrogels modified with laminin

The repair of brain lesion by implantation of hyaluronic acid hydrogels modified with laminin

A review of published reports on neuroprotection in spinal cord injury

KDI tripeptide of γ1 laminin protects rat dopaminergic neurons from 6‐OHDA induced toxicity

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