Improvement of BDNF signalling by P42 peptide in Huntington's disease (original) (raw)

2018, Human molecular genetics

Huntington's disease (HD) is caused by a mutation in the Huntingtin (HTT) protein. We previously reported that the 23aa peptide of HTT protein, P42, is preventing HD pathological phenotypes, such as aggregation, reduction of motor performances and neurodegeneration. A systemic treatment with P42 during the pre-symptomatic phase of the disease showed therapeutic potential in R6/2 mice. We here tested P42 effects when administered during the post-symptomatic phase. The P42 treatment alleviated deficits in motor performances, even when symptoms have already started. Because changes in the level and activity of brain-derived neurotrophic factor (BDNF) have been shown to play a central role in HD, we analysed the influence of P42 on BDNF deficit and associated phenotypes. Our data suggest that P42 is involved in the spatio-temporal control of bdnf and trkB mRNA and their protein levels. Related to this enhancement of BDNF-TrkB signalling, R6/2 mice treated with P42, exhibit reduced a...