Peptide HLDF-6 Exhibits Neuroprotective Activity in Neurodegenerative Diseases

The review is devoted to the analysis of published data on the normalizing and protective activity of the neuroprotective peptide HLDF-6 family. The peptide HLDF-6 (TGENHR) corresponds to fragment 41-46 of the protein differentiation factor HLDF (Human Leukemia Differentiation Factor). The neuroprotective peptide HLDF-6 and its analogue peptide HLDF-6-H (TGEXHR, where X is Hse) exhibit normalizing pharmacological activity, the targets of which are NMDA and metabotropic glutamate, serotonin and opioid systems, interacting with which the neuroprotective, nootropic, anxiolytic, differentiating, antitumor and anti-aging activity of these peptides is realized. In cellular and experimental models of Alzheimer’s disease induced by the introduction of beta-amyloid peptide Ab25–35, as well as a transgenic model of Alzheimer’s disease using B6C3-Tg(APPswe,PSEN1de9)85Dbo (Tg+) mice, the HLDF-6 peptide exhibits neuroprotective and nootropic activity. Chronic use of HLDF-6 peptide at a dose of 250 mg/kg is accompanied by a neuroprotective effect, normalizes steroidogenesis and effectively stimulates the performance of cognitive tasks. In an experimental model of Parkinson’s disease (PD), HLDF-6-H peptide exhibits neuroprotective, anxiolytic and antidepressant activity. Chronic use of HLDF-6-H peptide (intranasally, 3 weeks, 300 mg/kg/day) restores the level of dopamine and its turnover in the striatum, leads to overcoming motor dysfunctions, normalizes the levels of neurotrophin mRNA BDNF and inflammatory mediators TGFβ1, IL-1β and IFNg in parts of the brain, and also normalizes the concentrations of steroids and inflammatory factors in the bloodstream. The peptide HLDF-6-H has therapeutic potential for the creation of a pharmaceutical drug on its basis for the treatment of PD.