Mucuna pruriens (Velvet bean) rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson's disease.

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-conta...

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Autores principales: Simone Poddighe, Francescaelena De Rose, Roberto Marotta, Roberta Ruffilli, Maura Fanti, Pietro Paolo Secci, Maria Cristina Mostallino, Maria Dolores Setzu, Maria Antonietta Zuncheddu, Ignazio Collu, Paolo Solla, Francesco Marrosu, Sanjay Kasture, Elio Acquas, Anna Liscia
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Publicado: Public Library of Science (PLoS) 2014
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spelling oai:doaj.org-article:0421bc6e351f4e948131a0aebfbe03752021-11-25T05:55:28ZMucuna pruriens (Velvet bean) rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson's disease.1932-620310.1371/journal.pone.0110802https://doaj.org/article/0421bc6e351f4e948131a0aebfbe03752014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0110802https://doaj.org/toc/1932-6203The 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.Simone PoddigheFrancescaelena De RoseRoberto MarottaRoberta RuffilliMaura FantiPietro Paolo SecciMaria Cristina MostallinoMaria Dolores SetzuMaria Antonietta ZunchedduIgnazio ColluPaolo SollaFrancesco MarrosuSanjay KastureElio AcquasAnna LisciaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 10, p e110802 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Simone Poddighe
Francescaelena De Rose
Roberto Marotta
Roberta Ruffilli
Maura Fanti
Pietro Paolo Secci
Maria Cristina Mostallino
Maria Dolores Setzu
Maria Antonietta Zuncheddu
Ignazio Collu
Paolo Solla
Francesco Marrosu
Sanjay Kasture
Elio Acquas
Anna Liscia
Mucuna pruriens (Velvet bean) rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson's disease.
description 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.
format article
author Simone Poddighe
Francescaelena De Rose
Roberto Marotta
Roberta Ruffilli
Maura Fanti
Pietro Paolo Secci
Maria Cristina Mostallino
Maria Dolores Setzu
Maria Antonietta Zuncheddu
Ignazio Collu
Paolo Solla
Francesco Marrosu
Sanjay Kasture
Elio Acquas
Anna Liscia
author_facet Simone Poddighe
Francescaelena De Rose
Roberto Marotta
Roberta Ruffilli
Maura Fanti
Pietro Paolo Secci
Maria Cristina Mostallino
Maria Dolores Setzu
Maria Antonietta Zuncheddu
Ignazio Collu
Paolo Solla
Francesco Marrosu
Sanjay Kasture
Elio Acquas
Anna Liscia
author_sort Simone Poddighe
title Mucuna pruriens (Velvet bean) rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson's disease.
title_short Mucuna pruriens (Velvet bean) rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson's disease.
title_full Mucuna pruriens (Velvet bean) rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson's disease.
title_fullStr Mucuna pruriens (Velvet bean) rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson's disease.
title_full_unstemmed Mucuna pruriens (Velvet bean) rescues motor, olfactory, mitochondrial and synaptic impairment in PINK1B9 Drosophila melanogaster genetic model of Parkinson's disease.
title_sort mucuna pruriens (velvet bean) rescues motor, olfactory, mitochondrial and synaptic impairment in pink1b9 drosophila melanogaster genetic model of parkinson's disease.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/0421bc6e351f4e948131a0aebfbe0375
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