title: Differential effects of phytotherapic preparations in the hSOD1 Drosophila melanogaster model of ALS.
abstract: The present study was aimed at characterizing the effects of Withania somnifera (Wse) and Mucuna pruriens (Mpe) on a Drosophila melanogaster model for Amyotrophic Lateral Sclerosis (ALS). In particular, the effects of Wse and Mpe were assessed following feeding the flies selectively overexpressing the wild human copper, zinc-superoxide dismutase (hSOD1-gain-of-function) in Drosophila motoneurons. Although ALS-hSOD1 mutants showed no impairment in life span, with respect to GAL4 controls, the results revealed impairment of climbing behaviour, muscle electrophysiological parameters (latency and amplitude of ePSPs) as well as thoracic ganglia mitochondrial functions. Interestingly, Wse treatment significantly increased lifespan of hSDO1 while Mpe had not effect. Conversely, both Wse and Mpe significantly rescued climbing impairment, and also latency and amplitude of ePSPs as well as failure responses to high frequency DLM stimulation. Finally, mitochondrial alterations were any more present in Wse- but not in Mpe-treated hSOD1 mutants. Hence, given the role of inflammation in the development of ALS, the high translational impact of the model, the known anti-inflammatory properties of these extracts, and the viability of their clinical use, these results suggest that the application of Wse and Mpe might represent a valuable pharmacological strategy to counteract the progression of ALS and related symptoms.
authors.affiliation: University of Cagliari, Department of Biomedical Sciences, Monserrato, 09042, Italy.
authors.forename: Francescaelena
authors.initials: F
authors.lastname: De Rose
authors.affiliation: Istituto Italiano di Tecnologia (IIT), Department of Nanochemistry, Genova, 16163, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Marotta
authors.affiliation: National Research Council (CNR), Institute of Neuroscience, Monserrato, 09042, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Talani
authors.affiliation: Istituto Italiano di Tecnologia (IIT), Department of Nanochemistry, Genova, 16163, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Catelani
authors.affiliation: University of Cagliari, Department of Biomedical Sciences, Monserrato, 09042, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Solari
authors.affiliation: University of Cagliari, Department of Public Health, Clinical and Molecular Medicine, Monserrato, 09042, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Poddighe
authors.affiliation: University of Cagliari, Department of Public Health, Clinical and Molecular Medicine, Monserrato, 09042, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Borghero
authors.affiliation: University of Cagliari, Department of Public Health, Clinical and Molecular Medicine, Monserrato, 09042, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Marrosu
authors.affiliation: University of Cagliari, Department of Life and Environmental Sciences, Cagliari, 09124, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Sanna
authors.affiliation: Pinnacle Biomedical Research Institute, Bhopal, 462003, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kasture
authors.affiliation: University of Cagliari, Department of Life and Environmental Sciences, Cagliari, 09124, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Acquas
authors.affiliation: University of Cagliari, Department of Biomedical Sciences, Monserrato, 09042, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Liscia
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000818:Animals; D030801:Animals, Genetically Modified / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D005071:Evoked Potentials / Q000187:drug effects; D005724:Ganglia / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D008136:Longevity / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009046:Motor Neurons / Q000378:metabolism; D031299:Mucuna / Q000737:chemistry / Q000378:metabolism; D016296:Mutagenesis; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D032341:Withania / Q000737:chemistry / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C557617:GAL4 protein, Drosophila; D010936:Plant Extracts; D014157:Transcription Factors; D000072105:Superoxide Dismutase-1