Immunomodulatory properties of hempseed oligopeptides in an LRRK2-associated Parkinson's disease animal model†

Parkinson's disease (PD) is the second most common neurodegenerative disease, with genetic factors like mutations in the LRRK2 gene being a key cause of late-onset autosomal dominant parkinsonism. Nutritional strategies, such as using bioactive peptides with anti-inflammatory properties from sources like hemp protein, are gaining interest as an alternative to pharmacological therapies. In this study, we used an LRRK2-associated PD mouse model to test the efficacy of a hempseed protein hydrolysate (HPH60A + 15F) with antioxidant and anti-inflammatory properties. Mice were given HPH60A + 15F (10 mg kg⁻¹ day⁻¹) orally for 7 days. After treatment, brain tissue and macrophages were analyzed to assess neuroinflammation markers. Additionally, the neuroavailable peptidome was characterized using an in vitro model simulating the intestinal and blood–brain barriers. The oral treatment has been shown to reduce protein aggregates of α-syn, CD68, iNOS, and COX2 in the brain. The treatment also significantly lowered TNF-α gene expression in the striatum, with a notable reduction in the gene expression of other pro-inflammatory cytokines in bone marrow-derived macrophages (BMDMs), such as IL-1β or IL-6. The peptide TVTAMNVVYALK was proposed as a potential highly active peptide, able to exert anti-inflammatory effects in the brain. The results have shown that HPH60A + 15F is capable of alleviating neuroinflammation by reducing the expression of pro-inflammatory cytokines, which could have promising effects in PD.