The Flavonoid Agathisflavone from Poincianella pyramidalis Prevents Aminochrome Neurotoxicity
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The Flavonoid Agathisflavone from Poincianella pyramidalis Prevents Aminochrome Neurotoxicity Cleonice Creusa Santos 1 & Patricia Muñoz 2 & Áurea Maria A. N. Almeida 1 & Juceni Pereira de Lima David 3 & Jorge Mauricio David 4 & Silvia Lima Costa 1 & Juan Segura-Aguilar 2 & Victor Diogenes Amaral Silva 1 Received: 30 March 2020 / Revised: 26 May 2020 / Accepted: 7 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Flavonoids have been suggested to protect dopaminergic neurons in Parkinson’s disease based on studies that used exogenous neurotoxins. In this study, we tested the protective ability of agathisflavone in SH-SY5Y cells exposed to the endogenous neurotoxin aminochrome. The ability of aminochrome to induce loss of lysosome acidity is an important mechanism of its neurotoxicity. We demonstrated that the flavonoid inhibited cellular death and lysosomal dysfunction induced by aminochrome. In addition, we demonstrated that the protective effect of agathisflavone was suppressed by antagonists of estrogen receptors (ERα and ERβ). These results suggest lysosomal protection and estrogen signaling as mechanisms involved in agathisflavone neuroprotection in a Parkinson’s disease study model. Keywords Parkinson’s disease . Dopamine . Flavonoid . Neuroprotection
Introduction The discovery of genes associated with familial forms of Parkinson’s disease has had a great impact on the basic research for the understanding of their role in the neurodegeneration of nigrostriatal dopaminergic neurons containing neuromelanin. However, mutations in these genes, which include alpha-synuclein, pink-1, parkin, DJ-1, and ATP13A2 that encodes for a component of the lysosomal acidification machinery, cannot explain the degenerative process in the sporadic form of the disease. They provide important
* Juan Segura-Aguilar [email protected] * Victor Diogenes Amaral Silva [email protected] 1
Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia 40110-100, Brazil
2
Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Independencia, 1027 Santiago, Chile
3
Department of Medication, Faculty of Pharmacy, Federal University of Bahia, Salvador, Bahia 40170-290, Brazil
4
Department of General and Inorganic Chemistry, Institute of Chemistry, Federal University of Bahia, Salvador, Bahia, Brazil
information, and it is generally accepted that the aggregation of alpha-synuclein, dysfunction of protein degradation, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress, and neuroinflammation are involved in the degeneration of the nigrostriatal dopaminergic neurons (KalinderI et al. 2016; Kazlauskaite and Muqit 2015; Klein and Mazzulli 2018; Hopfner et al. 2020). Lysosome dysfunction appears to be also associated with idiopathic Parkinson’s disease since the mutation in GBA1, a gene that encodes for the lysosomal β-glucocerebro
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