A phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation and improve motor behavior in models of huntingtonʼs disease

Huntingtonʼs disease (HD) is an autosomal–dominant inherited neurological disorder caused by an unstable trinucleotide CAG repeat expansion at the N-terminus of gene encoding the huntingtin protein (Htt) [1]. The mutation results in Htt proteins with an abnormal length of polyglutamine (polyQ) repeats [2]. This abnormal aggregation of mutant Htt (mHtt) promotes neuronal dysfunction and death of medium spiny neurons in the striatum, resulting in altered motor control and cognitive function [2]. Effective treatments for HD are still pending. Previously, our group identified the presence of polyphenols in leaves from the Chilean-native berry Ugni molinae [3], [4], whose extracts showed a potent anti-aggregation activity in models of Alzheimerʼs disease [4]. However, beneficial effects of murtilla berry extracts were not investigated. Thus, we evaluated the efficacy of fruit extracts from different genotypes of U. molinae on reducing protein aggregation using cellular models of HD [5]. One extract (ETE 19 – 1) significantly reduced polyglutamine aggregation levels.

Aims: To determine the beneficial effect of ETE 19 – 1 extract in HD preclinicals models

Materials & Methods: R6/2 HD mouse model was treated with ETE-19-1 by Gavage daily for one month. We evaluated motor capacity by Rotarod test and protein aggregation in the brain tissue by western blot.

Results: HD preclinical models treated with ETE 19 – 1 shows that improves motor function and reduces protein aggregates in striatum.

Conclusion: Bioactive components in extracts from U. molinae berries have positive effects on HD. This demonstrates the potential effect of native polyphenols to treat neurodegenerative diseases associated with protein aggregates.

• References

• 1 Jimenez-Sanchez M. et al. Huntingtonʼs disease: mechanisms of pathogenesis and therapeutic strategies. Cold Spring Harb. Perspect. Med 2017; 7 (07) a024240
• 2 Elifani F. et al. Curcumin dietary supplementation ameliorates disease phenotype in an animal model of Huntingtonʼs disease. Human Molecular Genetics 2019; 28(23: 4012-4021.S
• 3 Peña-Cerda M, Arancibia-Radich J, Valenzuela-Bustamante P. et al. Phenolic composition and antioxidant capacity of Ugni molinae Turcz. leaves of different genotypes. Food Chem 2017; 215: 219-227
• 4 Jara-Moreno D, Castro-Torres RD, Ettcheto M. et al. The Ethyl Acetate Extract of Leaves of Ugni molinae Turcz. Improves Neuropathological Hallmarks of Alzheimerʼs Disease in Female APPswe/PS1 dE9 Mice Fed with a High Fat Diet. J Alzheimers Dis 2018; 66 (03) 1175-1191
• 5 Perez-Arancibia R, Ordonez JL, Rivas A. et al. A phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation in a cellular model of Huntingtonʼs disease. PLoS One 2021; 16 (07) e0254834

Publication History

Article published online:
12 December 2022