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Colangelo, A.M., Bianco, M.R., Vitagliano, L., Cavaliere, C., Cirillo, G., De Gioia, L., Diana, D., Colombo, D., Redaelli, C., Zaccaro, L., Morelli, G., Papa, M., Sarmientos, P., Alberghina, L. and Martegani, E. (2008) A New Nerve Growth Factor-Mimetic Peptide Active on Neuropathic Pain in Rats. The Journal of Neuroscience, 10, 2698-2709.
http://dx.doi.org/10.1523/JNEUROSCI.1508-04.2004

has been cited by the following article:

• TITLE: A Novel Dimeric Dipeptide Mimetic of the Nerve Growth Factor Exhibits Pharmacological Effects upon Systemic Administration and Has No Side Effects Accompanying the Neurotrophin Treatment

  AUTHORS: T. A. Gudasheva, P. Yu. Povarnina, T. A. Antipova, S. B. Seredenin

  KEYWORDS: Nerve Growth Factor, Mimetic, Dipeptide, GK-2, TrkA, PI3K/Akt, MAPK/Erk, Alzheimer’s Disease, Parkinson’s Disease, Stroke, Diabetes

  JOURNAL NAME: Neuroscience and Medicine, Vol.5 No.2, April 30, 2014

  ABSTRACT: The development of small molecule nerve growth factor (NGF) mimetics is a promising approach to overcome limitations in the use of the neurotrophin as a drug, which are poor pharmacokinetics and undesirable side effects. We designed dimeric dipeptide called GK-2 (bis(N-succinyl-L-glutamyl-L-lysine)hexametylendiamide) on the base of beta-turn sequence of NGF loop4 which most exposed to solvent and hence can play the major role in the interaction of NGF with the receptor. It was shown, that GK-2 stimulates phosphorylation of TrkA receptor, selectively activates PI3K/Akt signaling cascade that is important for cell survival, and does not activate MAPK/Erk pathway, associated not only with cell survival but also with cell differentiation. According to these data, GK-2 in vitro prevented H2O2- or MPTP- or glutamate-induced neuronal cell death at nanomolar concentrations, but did not provoke neurite outgrowth in PC12 cells. In vivo GK-2 exhibits therapeutic effects in models of Parkinson’s disease, Alzheimer’s disease, brain ischemia and diabetes mellitus. GK-2 shows activity in doses 0.01 - 5 mg/kg intraperitoneally and retains the activity after oral administration in dose 10 mg/kg. GK-2 has no side effects accompanying NGF treatment namely hyperalgesia and weight loss. Thus, the designed dimeric substituted dipeptide provides promising drug candidate and a molecular tool for investigating the possibility of divergence in NGF therapeutic and adverse effects.