Objective: The goal of this study is to investigate the effects of indole-derivative compound NC001-8 on neuroprotection in PD disease cell model.

Background: Parkinson’s disease (PD) is a common neurodegenerative disorder with selected loss of midbrain dopaminergic (DAergic) neurons. The lack of treatment to prevent the disease from progressing urges the development of new agents that may halt the rate of PD progression. Similar to other neurodegenerative diseases, there is increasing evidence that chaperones and oxidative stress participating to the pathogenesis of PD, while chaperone inducers and antioxidants may be relevant therapeutic strategies for PD. In previous study, we have found that indole derivative NC001-8, a Chinese herb, displayed prominent anti-oxidative and mitochondria biogenesis activities by up-regulatory of chaperones and/or autophagy in ataxia neurodegenerative cell models with ATXN3/Q75 or TBP/Q79 expression_1,2.

Methods: To identify the neuroprotection of NC001-8, we attempted to evaluate the chaperone and oxidative stress marker expressions, mitochondrial functions, cell survival, and apoptosis on DAergic cells derived from SH-SY5Y.

Results:         NC001-8 showed lower cytotoxicity and no impact on the neural induction by 12-O-tetradecanoyl- phorbol-13-acetate (TPA). However, treatment of NC001-8 not only gave rise to a remarkable reduce of ROS level but also was shown to a better survival rate in PD cell model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Moreover, the activation of cleavaged Caspase 3, the downstream of apoptotic pathway, was diminished through the cause of NC001-8.

        Subsequently, we used in-house Q-PCR array to find that NC001-8 elevated both of NRF2 and NQO1 on RNA and protein levels. Furthermore, an addition of NC001-8 for knockdown of NRF2 in PD cell model significantly eliminated oxidative stress and raised up the cell viability.

Conclusions:      Indole-derivative compound NC001-8 was capable of reducing ROS level and apoptotic activity in the PD cell model. The neuroprotective effect of NC001-8 was useful for maintaining cell survival. Therefore, these results might imply that the NC001-8 is able to develop a new therapeutics in treating PD as well.

References: 1. Kung, P. J. et al. Indole and synthetic derivative activate chaperone expression to reduce polyQ

aggregation in SCA17 neuronal cell and slice culture models. Drug Des Dev Ther 8, 1929-1939 (2014).

2. Lin, C. H. et al. The potential of indole and a synthetic derivative for polyQ aggregation reduction by enhancement of the chaperone and autophagy systems. ACS Chem Neurosci 5, 1063-1074 (2014).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuroprotection-of-indole-derivative-compound-nc001-8-in-parkinson-disease-cell-model-by-regulatory-of-nrf2-pathway/