Central penetration and stability of N-terminal tripeptide of insulin-like growth factor-I, glycine-proline-glutamate in adult rat

Baker, Ashleigh; Batchelor, D. C.; Thomas, Graham H.; Wen, Jingyuan; Rafiee, Masoumeh; Lin, Hai; Guan, Jian

doi:10.1016/j.npep.2004.11.001

Cited by 56 publications

(47 citation statements)

References 27 publications

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“…IGF-1 is a naturally occurring peptide in the central nervous system. GPE is the N-terminal tripeptide of IGF-1 that naturally cleaved in the plasma and brain tissue and has a neuroprotective effect in various ischemic brain injuries (Guan et al, 1999(Guan et al, , 2004Alexi et al, 1999;Aberg et al, 2000;O'Donnell et al, 2002;Baker et al, 2005). Therefore, proline, in normal levels, is an essential amino acid for neural protection against oxidative metabolites, and Pycs deficiency in old age in the inferior colliculus may contribute to both glutamate accumulation and proline deficiency.…”

Section: Discussionmentioning

confidence: 99%

Glutamate-related gene expression changes with age in the mouse auditory midbrain

et al. 2007

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Glutamate is the main excitatory neurotransmitter in both the peripheral and central auditory systems. Changes of glutamate and glutamate-related genes with age may be an important factor in the pathogenesis of age-related hearing loss -presbycusis. In this study, changes in glutamate-related mRNA gene expression in the CBA mouse inferior colliculus with age and hearing loss were examined and correlations were sought between these changes and functional hearing measures, such as the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs). Gene expression of 68 glutamate-related genes was investigated using both genechip microarray and real-time PCR (qPCR) molecular techniques for four different age/hearing loss CBA mouse subject groups. Two genes showed consistent differences between groups for both the genechip and qPCR. Pyrroline-5-carboxylate synthetase enzyme (Pycs) showed down-regulation with age and a highaffinity glutamate transporter (Slc1a3) showed up-regulation with age and hearing loss. Since Pycs plays a role in converting glutamate to proline, its deficiency in old age may lead to both glutamate increases and proline deficiencies in the auditory midbrain, playing a role in the subsequent inducement of glutamate toxicity and loss of proline neuroprotective effects. The up-regulation of Slc1a3 gene expression may reflect a cellular compensatory mechanism to protect against age-related glutamate or calcium excitoxicity.

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Section: Discussionmentioning

confidence: 99%

Glutamate-related gene expression changes with age in the mouse auditory midbrain

et al. 2007

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“…Glypromate, as an endogenous tripeptide cleaved from insulin-like growth factor-1 in the brain, has been reported to be neuroprotective against hypoxicischemic brain injury in experimental animals (Guan et al, 2004;Svedin et al, 2007). However, it rapidly degrades in plasma, resulting in low bioavailability in the brain (Baker et al, 2005;Batchelor et al, 2003). Glycyl-L-methylprolyl-L-glutamic acid is a peptidomimetic tripeptide (molecular weight 315.3 g/mol) designed to be more resistant to degradation by protease enzymes and has recently been shown to have significant neuroprotective effects in rat models of hypoxia/ischemia brain injury (Bickerdike et al, 2009) and penetrating ballistic-like brain injury (Lu et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

NNZ-2566, a Glypromate Analog, Attenuates Brain Ischemia-Induced Non-Convulsive Seizures in Rats

Williams

et al. 2009

J Cereb Blood Flow Metab

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Ischemic and traumatic brain injuries often induce non-convulsive seizures (NCSs), which likely contribute to the worsening of neurological outcomes. Here, we evaluated the effect of glycyl-Lmethylprolyl-L-glutamic acid (NNZ-2566) to lessen the severity of NCSs caused by permanent middle cerebral artery occlusion (pMCAo). Continuous electroencephalographic recordings were performed in rats during pMCAo. Glycyl-L-methylprolyl-L-glutamic acid (3, 10, or 100 mg/kg bolus followed by an infusion of a fixed dose of 3 mg/kg per hour for 12 h) was delivered at 20 mins after pMCAo (before the first NCS event) or delayed until immediately after the first NCS event occurred. Control rats received pMCAo and saline treatment. The results revealed that 91% of the salinetreated animals had NCSs (23 episodes per rat and 1238 secs per rat) with an onset latency of 35 mins after injury. When NNZ-2566 was administered before the NCS events, it dose-dependently reduced the NCS incidence to 36%-80%, decreased NCS frequency to 5-16 episodes per rat, and shortened the total duration of NCS to 251-706 secs per rat. The two high doses significantly reduced the infarct volume by 28%-30%. Delayed treatment also attenuated NCS duration but had no effect on the infarct volume. Results indicate that NNZ-2566 possesses a unique therapeutic potential as a safe prophylactic agent that synergistically provides neuroprotection and reduces injury-induced seizures.

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“…Unlike BDNF, IGF-1 is capable of crossing the blood-brain barrier, particularly in its tri-peptide form (1-3)IGF-1 (29), where it retains strong neurotrophic efficacy (22,30,31). IGF-1 signaling thus offers an attractive target for engaging key molecular pathways to potentially stimulate synaptic maturation and reverse the RTT phenotype, in a format that is more amenable to therapeutic administration to RTT patients.…”

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confidence: 99%

Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice

Tropea

Giacometti

Wilson

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

529

442

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Central penetration and stability of N-terminal tripeptide of insulin-like growth factor-I, glycine-proline-glutamate in adult rat

Cited by 56 publications

References 27 publications

Glutamate-related gene expression changes with age in the mouse auditory midbrain

Glutamate-related gene expression changes with age in the mouse auditory midbrain

NNZ-2566, a Glypromate Analog, Attenuates Brain Ischemia-Induced Non-Convulsive Seizures in Rats

Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice

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