NeuralCipher Research overview
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Abstract Parkinson’s disease (PD) is characterised by the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies containing α-synuclein (α-syn). PC12 cells are commonly used in cellular PD models. Neurocreen-1 cells (NS-1, a variant of PC12 cells) have a reduced doubling time and exhibit an enhanced neuronal phenotype compared to its parental PC12 cell line. This study aimed to develop a PD model with NS-1 cells based on the neurotoxin 6-hydroxydopamine (6-OHDA). Firstly, we investigated the expression of (endogenous) wild-type α-syn and pathological phosphorylated α-syn (pSer129-α-syn) in 6-OHDA-treated NS-1 cells via western blotting. However, wild type or pSer129-α-syn could not be immunodetected. Next, we examined the caspase-dependent apoptotic pathway in NS-1 cells treated with 6-OHDA. Cell viability was reduced, with significant activation of caspase-3 and -7. We validated this model by testing the effects of xanthones, a class of phytochemicals with reported neuroprotective properties. Gamma-mangostin at 10 nM increased cell viability with significant inhibition of caspase 3/7 activity, while beta-mangostin gave a lower effect. Lastly, we investigated the antiparkinsonian properties of lesser-studied xanthones: brasixanthone B, ananixanthone, thwaitesixanthone, trapezifolixanthone, and beta-mangostin. NS-1 cells replicated the effects of the neurotoxin 6-OHDA seen in parental PC12 cells. Of the lesser-studied xanthones, brasixanthone B and ananixanthone gave the greatest antiapoptotic activity in the PD model. We make the first report that brasixanthone B and thwaitesixanthone are neuroprotective. NS-1 is a fast-growing and adherent cell line with neuronal characteristics useful as an in vitro PD model in screening compounds for antiapoptotic effects, but unsuitable for modelling α-synucleinopathy.
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