A bioactive compound present in raspberries called salidroside can prevent the cellular toxicity that occurs as a consequence of protein accumulation in certain neurodegenerative diseases, including Huntington’s disease, a study reports.
The pharmacological properties of berries have long been acknowledged. Berries contain an extended repertoire of (poly)phenol molecules, which are known to provide protection against oxidative stress — an imbalance between the production of free radicals and the ability of cells to detoxify them, leading to cellular damage as a consequence of high levels of oxidant molecules.
Recently, there is increasing evidence that natural phenols in berries also have protective effects against metabolic disorders such as diabetes and obesity and against neurodegenerative diseases.
The loss of specific brain cells in several neurodegenerative diseases is often associated with the accumulation of disease-specific toxic protein aggregations.
(Poly)phenols have been shown to reduce the harmful effects of protein aggregation in neurodegenerative diseases, “rendering this group of natural products a promising source of compounds for ND [neurodegenerative disease] treatment,” the researchers wrote.
The researchers tested the activity of (poly)phenol-enriched extracts from the European raspberry, called Rubus idaeus, against the major neurodegenerative diseases — Alzheimer’s, Parkinson’s, Huntington’s and amyotrophic lateral sclerosis (ALS) — using a yeast-based screening model.
Yeast is a valuable organism model due to its easy accessibility, manipulation, and high degree of resemblance to biological processes in humans.
Yeast were modified to produce disease-specific protein aggregations in a controlled manner. Their ability to survive and proliferate was evaluated in the presence or absence of different raspberry-derived compounds.
R. idaeus-derived extracts were protective against the cytotoxic effects of protein aggregation in the context of Huntington’s but not other neurodegenerative diseases. Surprisingly, these effects were still observed when yeast were pretreated with the compound, before inducing protein aggregation.
In the case of Huntington’s, a mutation in the gene that provides instructions for making the huntingtin (HTT) protein leads to the accumulation of a mutant and toxic form of HTT in nerve cells. Accumulation of this toxic form of HTT results in oxidative damage, which, in turn, leads to cell death.
Although R. idaeus was not able to alter the levels and cellular localization of protein aggregation, the extract was able to restore redox homeostasis — the balance between oxidant and antioxidant species — that is impaired as a consequence of oxidative damage.
Further investigation revealed that a single molecule present in R. idaeus, called salidroside, was responsible for these protective effects.
However, red raspberries contain a limited amount of salidroside, and its extraction process faces several challenges. Moreover, “it has to be ensured that salidroside levels are consistent across season and plant growth locations, and that extraction methods are available to purify salidroside,” according to the researchers.
As a result, other strategies for salidroside large-scale production are of utmost importance in pursuing its pharmacological value.
The team engineered two microorganisms, namely S. cerevisiae (a yeast) and C. glutamicum and E. coli (bacteria), to establish a salidroside biosynthetic pathway. In other words, these microorganisms were altered to be able to produce this compound in a fast and efficient manner.
Salidroside produced with S. cerevisiae or C. glutamicum had very similar protective activities to that of the commercial, chemically synthesized compound.
Future studies must validate salidroside “in cellular models with a higher degree of complexity and in pre-clinical animal models to really assess its pharmaceutical potential,” the researchers concluded.
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