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Extracts from two ubiquitous Mediterranean plants ameliorate cellular and animal models of neurodegenerative proteinopathies
- Source :
- Neuroscience Letters. 638:12-20
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- A signature feature of age-related neurodegenerative proteinopathies is the misfolding and aggregation of proteins, typically amyloid-β (Aβ) in Alzheimer's disease (AD) and α-synuclein (α-syn) in Parkinson's disease (PD), into soluble oligomeric structures that are highly neurotoxic. Cellular and animal models that faithfully replicate the hallmark features of these disorders are being increasing exploited to identify disease-modifying compounds. Natural compounds have been identified as a useful source of bioactive molecules with promising neuroprotective capabilities. In the present report, we investigated whether extracts derived from two ubiquitous Mediterranean plants namely, the prickly pear Opuntia ficus-indica (EOFI) and the brown alga Padina pavonica (EPP) alleviate neurodegenerative phenotypes in yeast (Saccharomyces cerevisiae) and fly (Drosophila melanogaster) models of AD and PD. Pre-treatment with EPP or EOFI in the culture medium significantly improved the viability of yeast expressing the Arctic Aβ42 (E22G) mutant. Supplementing food with EOFI or EPP dramatically ameliorated lifespan and behavioural signs of flies with brain-specific expression of wild-type Aβ42 (model of late-onset AD) or the Arctic Aβ42 variant (model of early-onset AD). Additionally, we show that either extract prolonged the survival of a PD fly model based on transgenic expression of the human α-syn A53T mutant. Taken together, our findings suggest that the plant-derived extracts interfere with shared mechanisms of neurodegeneration in AD and PD. This notion is strengthened by evidence demonstrating that EOFI and to a greater extent EPP, while strongly inhibiting the fibrillogenesis of both Aβ42 and α-syn, accumulate remodelled oligomeric aggregates that are less effective at disrupting lipid membrane integrity. Our work therefore opens new avenues for developing therapeutic applications of these natural plant extracts in the treatment of amyloidogenic neurodegenerative disorders.
- Subjects :
- 0301 basic medicine
Transgene
ved/biology.organism_classification_rank.species
Mutant
Saccharomyces cerevisiae
Biology
Phaeophyta
Neuroprotection
03 medical and health sciences
0302 clinical medicine
Alzheimer Disease
medicine
Animals
Humans
Model organism
Amyloid beta-Peptides
Plant Extracts
ved/biology
General Neuroscience
Neurodegeneration
Opuntia
Neurodegenerative Diseases
Parkinson Disease
medicine.disease
biology.organism_classification
Phenotype
Peptide Fragments
Drosophila melanogaster
Neuroprotective Agents
030104 developmental biology
Biochemistry
Mutation
alpha-Synuclein
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 03043940
- Volume :
- 638
- Database :
- OpenAIRE
- Journal :
- Neuroscience Letters
- Accession number :
- edsair.doi.dedup.....b65df95d340f06f2bde3ccad7e6785b7