Short Lecture “Therapeutic potential of Murtilla extracts in ameliorating Huntington's disease symptoms in preclinical models”

Huntington’s 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). The mutation results in the production of abnormal aggregation of Htt (mHtt) which promotes neuronal dysfunction and death of medium spiny neurons in striatum, resulting in altered motor control and cognitive function. Effective treatments for HD are still pending. Previously, our group identified the presence of polyphenols in leaves from the Chilean-native berry Ugni molinae, whose extracts showed a potent anti-aggregation activity in models of Alzheimer´s disease. We evaluated the efficacy of 8 fruit extracts from different genotypes of U. molinae on reducing protein aggregation using cellular models of HD. One extract, ETE 19-1, significantly reduced polyglutamine aggregation levels. We aimed to investigate the effect of the 19-1 extract on preclinical models of Huntington's disease, both at the brain and intestinal levels. A R6/2 HD mouse model was treated with ETE-19-1 by gavage daily for one month. We evaluated motor capacity by Rotarod test, protein aggregation and neuroinflammation in the brain tissue and intestinal damage. Our results in HD preclinical models treated with ETE 19-1 shows that it improves motor function, reduces protein aggregates and neuroinflammation in striatum, and provides additional relief to the intestinal damage present in R6/2 mice. Bioactive components in extracts from U. molinae berries have positive effects on HD. This demonstrates the potential effect of native berries to treat neurodegenerative diseases associated with protein aggregates ([Fig. 1]).

Fig. 1 ETE 19-1 chronic oral treatment improves motor behavior and decreases the levels of HTT in the striatum of R6/2 mouse models of HD. a) The Rotarod motor test consists of a rod that rotates at a set speed for a specified time. The mice are placed on the spinning rod, which causes the mice to start running. This test was carried out at a constant speed of 4 rpm, for a total time of 5 min (n=10 animals per group). b) The total time (in seconds) that each animal spent on the wheel was recorded. (**p=0.0067;****p = < 0.0001). Healthy WT mice, R6/2 mice (without polyphenols) and R6/2 mice with polyphenols (ETE 19-1). c) The effect ETE 19-1 on HTT levels was analyzed by Western blot. B-Actin expression was monitored as a loading control d) Quantification of HMW levels of HTT (*p=0.0101).

 

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Artikel online veröffentlicht:
16. November 2023