Dataset Information

Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK.

ABSTRACT: Parkinson's disease (PD) represents one of the most common neurodegenerative disorders, characterized by a dopamine (DA) deficiency in striatal synapses and misfolded toxic α-synuclein aggregates with concomitant cytotoxicity. In this regard, the misfolded proteins accumulation in neurodegenerative disorders induces a remarkable perturbations of endoplasmic reticulum (ER) homeostasis leading to persistent ER stress, which in turn, effects protein synthesis, modification, and folding quality control. A large body of evidence suggests that natural products target the ER stress signaling pathway, exerting a potential action in cancers, diabetes, cardiovascular and neurodegenerative diseases. This study aims to assess the neuroprotective effect of cocoa extract and its purified fractions against a cellular model of Parkinson's disease represented by 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma. Our findings demonstrate, for the first time, the ability of cocoa to specifically targets PERK sensor, with significant antioxidant and antiapoptotic activities as both crude and fractioning extracts. In addition, cocoa also showed antiapoptotic properties in 3D cell model and a notable ability to inhibit the accumulation of α-synuclein in 6-OHDA-induced cells. Overall, these results indicate that cocoa exerts neuroprotective effects suggesting a novel possible strategy to prevent or, at least, mitigate neurodegenerative disorders, such as PD.

SUBMITTER: Vestuto V

PROVIDER: S-EPMC9405838 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK.

Vestuto Vincenzo V Amodio Giuseppina G Pepe Giacomo G Basilicata Manuela Giovanna MG Belvedere Raffaella R Napolitano Enza E Guarnieri Daniela D Pagliara Valentina V Paladino Simona S Rodriquez Manuela M Bertamino Alessia A Campiglia Pietro P Remondelli Paolo P Moltedo Ornella O

Biomedicines 20220818 8

Parkinson's disease (PD) represents one of the most common neurodegenerative disorders, characterized by a dopamine (DA) deficiency in striatal synapses and misfolded toxic α-synuclein aggregates with concomitant cytotoxicity. In this regard, the misfolded proteins accumulation in neurodegenerative disorders induces a remarkable perturbations of endoplasmic reticulum (ER) homeostasis leading to persistent ER stress, which in turn, effects protein synthesis, modification, and folding quality cont ...[more]

PMID: 36009556

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Project description:Allopregnanolone (APα), as a functional neurosteroid, exhibits the neuroprotective effect on neurodegenerative diseases such as Parkinson's disease (PD) through γ-aminobutyric acid A receptor (GABAAR), but it has not been completely understood about its molecular mechanisms. In order to investigate the neuroprotective effect of APα, as well as to clarify its possible molecular mechanisms, SH-SY5Y neuronal cell lines were incubated with 6-hydroxydopamine (6-OHDA), which has been widely used as an in vitro model for PD, along with APα alone or in combination with GABAAR antagonist (bicuculline, Bic), intracellular Ca2+ chelator (EGTA) and voltage-gated L-type Ca2+ channel blocker (Nifedipine). The viability, proliferation, and differentiation of SH-SY5Y cells, the expression levels of calmodulin (CaM), Ca2+/calmodulin-dependent protein kinase II δ3 (CaMKIIδ3), cyclin-dependent kinase-1 (CDK1) and brain-derived neurotrophic factor (BDNF), as well as the interaction between CaMKIIδ3 and CDK1 or BDNF, were detected by morphological and molecular biological methodology. Our results found that the cell viability and the number of tyrosine hydroxylase (TH), bromodeoxyuridine (BrdU) and TH/BrdU-positive cells in 6-OHDA-treated SH-SY5Y cells were significantly decreased with the concomitant reduction in the expression levels of aforementioned proteins, which were ameliorated following APα administration. In addition, Bic could further increase the number of TH or BrdU-positive cells as well as the expression levels of aforementioned proteins except for TH/BrdU-double positive cells, while EGTA and Nifedipine could attenuate the expression levels of CaM, CaMKIIδ3 and BDNF. Moreover, there existed a direct interaction between CaMKIIδ3 and CDK1 or BDNF. As a result, APα-induced an increase in the number of TH-positive SH-SY5Y cells might be mediated through GABAAR via Ca2+/CaM/CaMKIIδ3/BDNF (CDK1) signaling pathway, which would ultimately facilitate to elucidate PD pathogenesis and hold a promise as an alternative therapeutic target for PD.

Dataset Information

Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK.

Publications

Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK.

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