Neuroprotective Effect of the Hexapeptide HLDF-6 on Rat Hippocampal Neurons on the In Vivo and In Vitro Models of Alzheimer's Disease

I. A. Kostanyan^a,#, S. S. Zhokhov^a, Z. I. Storozheva^b, A. T. Proshin^b, E. A. Surina^a, I. I. Babichenko^c, V. V. Sherstnev^b, and V. M. Lipkin^a

^# Phone: +7 (495) 336-5511; fax: +7 (495) 336-6166; e-mail: iakost@mail.ibch.ru
^a Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997 Russia
^b Anokhin Institute of Normal Physiology, Russian Academy of Medical Sciences, Mokhovaya ul. 14, Moscow, 103009 Russia
^c Russian Peoples' Friendship University, ul. Miklukho-Maklaya 6, Moscow, 117198 Russia

Received July 11, 2005; in final form, August 2, 2005

Abstract: The neuroprotective effect of Thr-Gly-Glu-Asn-His-Arg hexapeptide (HLDF-6), a biologically active fragment of the differentiation factor of human leukemia cells (HLDF), was demonstrated on models of Alzheimer's disease in vivo and in vitro. The syndromes of this pathology were induced in male rats by injection of beta-amyloid peptide (25--35) and ibotenic acid into the hippocampus. HLDF-6 prevented loss of long-term memory and decrease in the exploration behavior of these animals and significantly decreased the number of pyknotic neurons in the CA1 area of the hippocampus. This peptide also exerts a protective effect in vitro on the primary cultures of the rat hippocampal and cerebellar neurons under conditions of the beta-amyloid toxicity. An increase in the dihydrotestosterone (DHT) content was demonstrated in the blood plasma of rats with the syndrome of Alzheimer's disease and in the medium of the culture of hippocampal neurons in the presence of the Aβ(25--35) peptide. HLDF-6 inhibited this increase in both cases. A probable mechanism of the neuroprotective effect of HLDF-6 was suggested as being connected to its possible effect on both the biosynthesis and the metabolism of sex steroid hormones.

Key words: Alzheimer's disease; dihydrotestosterone; hippocampus; HLDF differentiation factor, neuroprotective effect; peptide corresponding to the 25--35 sequence of beta-amyloid

Russian Journal of Bioorganic Chemistry 2006, 32 (4):360-367