Session Title: Therapy in Movement Disorders: Gene and Cell-Based Therapies
Session Time: 1:45pm-3:15pm
Location: Hall 3FG
Objective: To investigate if the protective effects of curcumin previously observed in SH-SY5Y cells are also found in patient-derived fibroblasts from Parkinson’s disease patients.
Background: Parkinson’s disease (PD) occurs in 1-2% of individuals older than 60 years and is recognized by the loss of balance, resting tremors and bradykinesia. Potential underlying mechanisms of PD include mitochondrial dysfunction, oxidative stress and abnormal protein processing. To date, no cure exists for PD while various drug treatments only treat the symptoms and not the underlying cause of the neurodegeneration. Therefore, there is a need for a therapy directed at the underlying mechanisms of PD. Curcumin is a polyphenol, attributed with antioxidant, anti-inflammatory and antimicrobial properties. A recent study by our group showed that curcumin protected against mitochondrial dysfunction and cell death in a siRNA-mediated knockdown of PINK1 in SH-SY5Y cells . The aim of this study was, therefore, to follow-up on the PINK1 cell model of PD and investigate the protective effect of curcumin in PD patient-derived fibroblasts.
Methods: Dermal fibroblasts were obtained from PD patients with LRRK2 genetic mutations. A MTT assay was used to determine the effect of paraquat and curcumin treatment on cell activity. Concentration and treatment duration curves for paraquat treatment were performed to obtain 50% cell viability loss in fibroblasts.
Results: We previously showed that paraquat (25 µM) decreased cell viability, increased apoptosis and disrupted mitochondrial function in the PINK1 SH-SY5Y cell model . Notably, curcumin rescued cell viability, decreased apoptosis and increased mitochondrial respiration in these cells . In the current study, we found that a higher concentration of paraquat (35 mM) was needed to decrease cell viability in the primary fibroblasts. Studies are in progress to determine whether we see the same protective effect of curcumin in the fibroblasts.
Conclusions: The preliminary results indicate that primary fibroblasts are less sensitive to paraquat toxicity, than SH-SY5Y cells. We previously showed that curcumin was protective in SH-SY5Y cells and it would be interesting to observe the effect in patient fibroblasts. Successful results for curcumin in fibroblasts can further elucidate the role of curcumin as a potential neuroprotective agent against cell loss in PD.
References: 1. van der Merwe C, van Dyk HC, Engelbrecht L, van der Westhuizen FH, Kinnear C, Loos B, Bardien S. Curcumin rescues a PINK1 knock down SH-SY5Y cellular model of Parkinson’s disease from mitochondrial dysfunction and cell death. Mol Neurobiol. 2017 May;54(4):2752-2762.
To cite this abstract in AMA style:S. Abrahams, C. vander Merwe, A. Neethling, J. Carr, S. Bardien. An investigation of the potential neuroprotective role of curcumin in Parkinson’s disease patient-derived fibroblasts [abstract]. Mov Disord. 2018; 33 (suppl 2). https://www.mdsabstracts.org/abstract/an-investigation-of-the-potential-neuroprotective-role-of-curcumin-in-parkinsons-disease-patient-derived-fibroblasts/. Accessed December 5, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/an-investigation-of-the-potential-neuroprotective-role-of-curcumin-in-parkinsons-disease-patient-derived-fibroblasts/