Lutein protects dopaminergic neurons against MPTP-induced apoptotic death and motor dysfunction by ameliorating mitochondrial disruption and oxidative stress Jagatheesan Nataraj 1 , Thamilarasan Manivasagam 1 , Arokiasamy Justin Thenmozhi 1 , Musthafa Mohammed Essa 2 1 Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalai Nagar 608 002, Tamilnadu, India, 2 Department of Food Science and Nutrition, CAMS, Sultan Qaboos University, Muscat, Oman Objective: Mitochondrial dysfunction and oxidative stress-mediated apoptosis plays an important role in various neurodegenerative diseases including Huntington’s disease, Parkinson’s disease (PD) and Alzheimer’s disease (AD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the most widely used neurotoxin mimics the symptoms of PD by inhibiting mitochondrial complex I that stimulates excessive intracellular reactive oxygen species (ROS) and finally leads to mitochondrial-dependent apoptosis. Lutein, a carotenoid of xanthophyll family, is found abundantly in leafy green vegetables such as spinach, kale and in egg yolk, animal fat and human eye retinal macula. Increasing evidence indicates that lutein has offers benefits against neuronal damages during diabetic retinopathy, ischemia and AD by virtue of its mitochondrial protective, antioxidant and anti-apoptotic properties. Methods: Male C57BL/6 mice (23-26 g) were randomized and grouped in to Control, MPTP, and Lutein treated groups. Results: Lutein significantly reversed the loss of nigral dopaminergic neurons by increasing the striatal dopamine level in mice. Moreover, lutein-ameliorated MPTP induced mitochondrial dysfunction, oxidative stress and motor abnormalities. In addition, lutein repressed the MPTP-induced neuronal damage/ apoptosis by inhibiting the activation of pro-apoptotic markers (Bax, caspases-3, 8 and 9) and enhancing anti-apoptotic marker (Bcl-2) expressions. Discussion: Our current results revealed that lutein possessed protection on dopaminergic neurons by enhancing antioxidant defense and diminishing mitochondrial dysfunction and apoptotic death, suggesting the potential benefits of lutein for PD treatment. Keywords: Parkinson’s disease, Mitochondrial dysfunction, Oxidative stress, Apoptosis and lutein Introduction Parkinson’ s disease (PD) is the second most prevalent and insidiously progressive neurodegenerative disease that mainly affects the elderly population worldwide. Pathogenesis of PD arises primarily by degeneration of dopaminergic nigrostriatal neurons and secondarily by complex pathological mechanisms including mito- chondrial dysfunction, oxidative stress and apoptotic cell death, resulting in motor dysfunctions such as tremor, rigidity, akinesia and postural reflexes. 1 MPTP causes destruction of dopaminergic neurons and serves as an excellent animal model that extensively mimics the symptoms of PD. After cross- ing blood–brain barrier (BBB), MPTP is converted to 1-methyl-4-phenylpyridinium (MPP + ), by mono- amine oxidase B, which enters into dopaminergic neurons specifically through the dopamine transpor- ter. Accumulation of MPP + , a toxic metabolite of MPTP, inhibits mitochondrial complex I of electron transport chain (ETC), 2 causing the generation of reactive oxygen species (ROS) and depletion of ATP, which ultimately leads to neuronal death. 3 The neuro- toxin induces apoptosis by downstream effects of ROS via sequential opening mitochondria permeability transition pore to release cytochrome c from mito- chondria into cytoplasm that activates pro-apoptotic caspases. 4 Correspondence to: T. Manivasagam, Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar 608 002, Tamilnadu, India, E-mail: mani_pdresearchlab@rediffmail.com © W. S. Maney & Son Ltd 2015 DOI 10.1179/1476830515Y.0000000010 Nutritional Neuroscience 2015 1