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.

The Interaction of Curcumin and Rosmarinic Acid with Non‐Amyloid‐Component Domain of Alpha‐Synuclein: A Molecular Dynamics Study

“…Also, previous investigations have shown that CUR neuroprotective properties in in‐vitro and in‐vivo PD models are consistent with several different environmental factors …”

Development of Therapeutics That Induce Mitochondrial Biogenesis for the Treatment of Acute and Chronic Degenerative Diseases

“…109 Pretreatment with 4 improves mitochondrial membrane potential, oxygen consumption rates, and survival in cellular models of Parkinson disease. 110 Compound 4 attenuates neuronal death and reduces infarct size following cerebral ischemia-reperfusion injury with concomitant increases in mitochondria and improvements in neurological function. 111 In animal models of metabolic syndrome, 4 restores hepatocyte mitochondrial function to reduce hepatosteatosis.…”

Curcumin Effectively Rescued Parkinson’s Disease‐Like Phenotypes in a Novel Drosophila melanogaster Model with dUCH Knockdown

“…In the dopaminergic cell lines MES23.5 and SH-SY5Y, curcumin treatments attenuated the neurotoxicity of 6-OHDA and improved cell viability by inhibiting increases in ROS levels, mitochondrial protection, and reducing p53-mediated apoptosis [ 22 , 23 ]. A recent study also reported that curcumin protected against mitochondrial dysfunction and cell death in PINK1 knockdown SH-SY5Y cells [ 24 ]. Moreover, curcumin had the potential not only to increase lifespan and locomotor abilities but also to decrease oxidative stress and DA neuron degeneration in rotenone-induced and human α -synuclein-expressing Drosophila models of PD [ 26 , 27 ].…”