title: Curcumin Rescues a PINK1 Knock Down SH-SY5Y Cellular Model of Parkinson's Disease from Mitochondrial Dysfunction and Cell Death.
abstract: Parkinson's disease (PD) is a neurodegenerative disorder characterised by the loss of dopaminergic neurons in the substantia nigra. Mutations in the PINK1 gene result in an autosomal recessive form of early-onset PD. PINK1 plays a vital role in mitochondrial quality control via the removal of dysfunctional mitochondria. The aim of the present study was to create a cellular model of PD using siRNA-mediated knock down of PINK1 in SH-SY5Y neuroblastoma cells The possible protective effects of curcumin, known for its many beneficial properties including antioxidant and anti-inflammatory effects, was tested on this model in the presence and absence of paraquat, an additional stressor. PINK1 siRNA and control cells were separated into four treatment groups: (i) untreated, (ii) treated with paraquat, (iii) pre-treated with curcumin then treated with paraquat, or (iv) treated with curcumin. Various parameters of cellular and mitochondrial function were then measured. The PINK1 siRNA cells exhibited significantly decreased cell viability, mitochondrial membrane potential (MMP), mitochondrial respiration and ATP production, and increased apoptosis. Paraquat-treated cells exhibited decreased cell viability, increased apoptosis, a more fragmented mitochondrial network and decreased MMP. Curcumin pre-treatment followed by paraquat exposure rescued cell viability and increased MMP and mitochondrial respiration in control cells, and significantly decreased apoptosis and increased MMP and maximal respiration in PINK1 siRNA cells. These results highlight a protective effect of curcumin against mitochondrial dysfunction and apoptosis in PINK1-deficient and paraquat-exposed cells. More studies are warranted to further elucidate the potential neuroprotective properties of curcumin.
authors.affiliation: Division of Molecular Biology & Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. celiavdm@sun.ac.za.
authors.forename: Celia
authors.identifier: 0000-0003-0198-2184
authors.initials: C
authors.lastname: van der Merwe
authors.affiliation: Human Metabolomics, Faculty of Natural Sciences, North West University, Potchefstroom, South Africa.
authors.forename: Hayley Christy
authors.initials: HC
authors.lastname: van Dyk
authors.affiliation: Cell Imaging Unit, Central Analytical Facility, Stellenbosch University, Cape Town, South Africa.
authors.forename: Lize
authors.initials: L
authors.lastname: Engelbrecht
authors.affiliation: Human Metabolomics, Faculty of Natural Sciences, North West University, Potchefstroom, South Africa.
authors.forename: Francois Hendrikus
authors.initials: FH
authors.lastname: van der Westhuizen
authors.affiliation: Division of Molecular Biology & Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.|SAMRC Centre for Tuberculosis Research and the DST/NRF Centre of Excellence for Biomedical TB Research, Stellenbosch University, Cape Town, South Africa.
authors.forename: Craig
authors.initials: C
authors.lastname: Kinnear
authors.affiliation: Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Ben
authors.initials: B
authors.lastname: Loos
authors.affiliation: Division of Molecular Biology & Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. sbardien@sun.ac.za.
authors.forename: Soraya
authors.initials: S
authors.lastname: Bardien
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002459:Cell Fusion; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D010101:Oxygen Consumption / Q000187:drug effects; D010269:Paraquat; D010300:Parkinson Disease / Q000201:enzymology* / Q000473:pathology*; D011494:Protein Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D003474:Curcumin; D010269:Paraquat; D011494:Protein Kinases; D034741:RNA, Small Interfering; D000099202:PTEN-Induced Putative Kinase
keywords: Apoptosis; Curcumin; Mitochondrial dysfunction; PINK1; Parkinson’s disease