Аннотация:The mechanisms of the neuroprotective action of the hexapeptides HLDF-6 and HLDF-6-H, derivatives of the fragment 41-46 of the Human Leukemia Differentiation Factor, were determined in an experimental MPTP model of Parkinson's disease (PD) in C57Bl/6 mice (two intraperitoneal injections of MPTP-HCl, 18 mg/kg, with an interval of 2 hours). For the analysis of motor disturbances in the preclinical stage of PD, the "Horizontal grid" test was used. It was found that chronic administration of peptides (intranasally, 3 weeks, 300 μg/kg/day) restored the level of dopamine and its turnover in the striatum, increased the level of serum estradiol and led to a significant improvement in motor dysfunctions. In addition, the peptides normalized the mRNA levels of the neurotrophin BDNF and inflammatory mediators TGFβ1, IL1β and IFNγ in the brain. The findings provide evidence that the HLDF-6 peptides have a therapeutic potential to treat PD. The neuroprotective mechanism may involve the normalizing estradiol levels and expression of key factors of neurotrophic support and neuroinflammation
