title: Mucuna pruriens (Velvet bean) rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson's disease.
abstract: The fruit fly Drosophila melanogaster (Dm) mutant for PTEN-induced putative kinase 1 (PINK1B9) gene is a powerful tool to investigate physiopathology of Parkinson's disease (PD). Using PINK1B9 mutant Dm we sought to explore the effects of Mucuna pruriens methanolic extract (Mpe), a L-Dopa-containing herbal remedy of PD. The effects of Mpe on PINK1B9 mutants, supplied with standard diet to larvae and adults, were assayed on 3-6 (I), 10-15 (II) and 20-25 (III) days old flies. Mpe 0.1% significantly extended lifespan of PINK1B9 and fully rescued olfactory response to 1-hexanol and improved climbing behavior of PINK1B9 of all ages; in contrast, L-Dopa (0.01%, percentage at which it is present in Mpe 0.1%) ameliorated climbing of only PINK1B9 flies of age step II. Transmission electron microscopy analysis of antennal lobes and thoracic ganglia of PINK1B9 revealed that Mpe restored to wild type (WT) levels both T-bars and damaged mitochondria. Western blot analysis of whole brain showed that Mpe, but not L-Dopa on its own, restored bruchpilot (BRP) and tyrosine hydroxylase (TH) expression to age-matched WT control levels. These results highlight multiple sites of action of Mpe, suggesting that its effects cannot only depend upon its L-Dopa content and support the clinical observation of Mpe as an effective medication with intrinsic ability of delaying the onset of chronic L-Dopa-induced long-term motor complications. Overall, this study strengthens the relevance of using PINK1B9 Dm as a translational model to study the properties of Mucuna pruriens for PD treatment.
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Poddighe
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Francescaelena
authors.initials: F
authors.lastname: De Rose
authors.affiliation: Electron Microscopy Lab, Nanochemistry Department, Istituto Italiano di Tecnologia, Genoa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Marotta
authors.affiliation: Electron Microscopy Lab, Nanochemistry Department, Istituto Italiano di Tecnologia, Genoa, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ruffilli
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Fanti
authors.affiliation: Institute of Neuroscience, National Research Council, Cagliari, Italy.
authors.forename: Pietro Paolo
authors.initials: PP
authors.lastname: Secci
authors.affiliation: Institute of Neuroscience, National Research Council, Cagliari, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mostallino
authors.affiliation: Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Setzu
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Zuncheddu
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Collu
authors.affiliation: Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Solla
authors.affiliation: Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Marrosu
authors.affiliation: Sanjivani College of Pharmaceutical Education and Research, Kopargaon, Ahmednagar, Maharashtra, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kasture
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy; Center of Excellence for the Study of Neurobiology of Addiction, University of Cagliari, Cagliari, Italy; National Institute of Neuroscience - INN, University of Cagliari, Cagliari, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Acquas
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Liscia
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D004594:Electrophysiology; D008124:Locomotion; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects*; D031299:Mucuna / Q000737:chemistry; D009154:Mutation; D009422:Nervous System Diseases / Q000188:drug therapy*; D010300:Parkinson Disease / Q000503:physiopathology; D010936:Plant Extracts / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012903:Smell / Q000187:drug effects*; D013569:Synapses / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D029721:Drosophila Proteins; D010936:Plant Extracts; D017346:Protein Serine-Threonine Kinases; D014446:Tyrosine 3-Monooxygenase; C534484:PINK1 protein, Drosophila; D000099202:PTEN-Induced Putative Kinase