Motoneuronotrophic factor analog GM6 reduces infarct volume and behavioral deficits following transient ischemia in the mouse

Abstract

Motoneuronotrophic factor (MNTF) is an endogenous neurotrophin that is highly specific for the human nervous system, and some of the observed effects of MNTF include motoneuron differentiation, maintenance, survival, and reinnervation of target muscles and organs. MNTF is a neuro-signaling molecule that binds to specific receptors. Using In Silico Analysis, one of the active sites of MNTF was identified as an analog of six amino acids (GM6). The effect of chemically synthesized GM6 on ischemic stroke was studied in the middle cerebral artery occlusion (MCAo) mouse model. Mice were subjected to 1 hour of ischemia followed by 24 hours of reperfusion. Mice were injected intravenously with a bolus of GM6, at various doses (1 and 5 mg/kg) immediately after the start of reperfusion and examined for changes in physiological parameters, neurological deficits and infarct volume. GM6 was able to penetrate the blood brain barrier, and at both 1 and 5 mg/kg showed a significant protection from infarct damage, which translated to improvement of neurological deficits. Administration of GM6 demonstrated no changes in HR, BP, pO2, pCO2, or pH. A significant increase over the control group in CBF after reperfusion was observed with GM6 administration, which helped to mitigate the ischemic effect caused by the blockage of blood flow. The time window of treatment was assessed at various times following cerebral ischemia with GM6 demonstrating a significant protective effect up to 6–12 hours post ischemia. In addition, GM6 increased neurogenesis, and decreased apoptosis and inflammation in the mouse brain following cerebral ischemic injury. These data suggest that GM6 is neuroprotective to the brain following IV injection in the mouse model of MCAo.

Nanoparticles for Targeted Delivery of Antioxidant Enzymes to the Brain after Cerebral Ischemia and Reperfusion Injury

“…Animals were subjected to 1 hour ischemia followed by 1 hour or 24 hours reperfusion. 34,35 Animals were randomly assigned to a control group (n ¼ 12) or groups (n ¼ 12) treated with an intracartoid injection of nanoparticles at 25 U of SOD activity per Nanoparticles and cerebral ischemia X Yun et al injection. Nanoparticles or liposomes were prepared as described above and the solution was stored at 41C.…”

In vitro biomimetic HPLC and in vivo characterisation of GM6, an endogenous regulator peptide drug candidate for amyotrophic lateral sclerosis

“…At four hours, the animals were sacrificed, and half of the brain was frozen for ELISA analysis. The detailed experimental process has been published previously [25].…”

ALSUntangled No. 34: GM604

“…Overview GM604 is a synthetic six-amino acid peptide fragment of a larger protein growth factor called motoneurotrophic factor (2).…”

“…PubMed searches of GM6 and GM604 identified only a single possibly relevant publication (2). In this study, GM604 or vehicle were administered to mice following an experimentally induced stroke and reperfusion.…”