1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is an environmental toxin which selectively induces oxidative damage and mitochondrial and proteasomal dysfunctions to dopaminergic neurons in the substantia nigra leading to Parkinsonian syndrome in animal models and humans. MPTP is one of the most widely used in vitro models to investigate the pathophysiology of Parkinson's disease (PD) and, screen for novel therapeutic compounds that can slow down or ameliorate this progressive degenerative disease. We investigated the therapeutic effect of pomegranate juice extracts (PJE), Helow, Malasi, Qusum, and Hamadh against MPTP-induced neurotoxicity in primary human neurons by examining extracellular LDH activity, intracellular NAD+ and ATP levels, and endogenous antioxidant levels including lipid peroxidation products, catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, and reduced glutathione (GSH) levels. MPTP induced a reduction in SOD and GPx activities and intracellular NAD+, ATP, and GSH levels parallel to an increase in extracellular LDH and CAT activities, although lipid peroxidation was not altered. We report that helow and malasi can ameliorate MPTP-induced neurotoxicity by attenuating the observed changes in redox function to a greater extent than qusum and hamedh. Selected PJE varieties may exhibit properties which may be of therapeutic value to slow down age-related degeneration and neurodegeneration in particular. 1. Introduction As the ageing population continues to grow at an alarming rate, the likelihood of people developing debilitating neurodegenerative deficits such as Parkinson’s disease (PD) is growing rapidly. PD represents the second most common neurological disorder after Alzheimer’s disease (AD), and it affects 2% of the population over the age of 60. PD is characterised by the chronic and progressive loss of dopaminergic neurons in the substantia nigra [1]. Although the etiology of PD is not yet known, current studies have suggested that oxidative stress may be a major player [2]. An imbalance between the formation of free radicals and reactive oxygen species (ROS) and the body’s endogenous antioxidant defense mechanisms has also been implicated in the pathogenesis of other neurodegenerative diseases such as AD, Huntington’s disease (HD), Pick’s disease, amyotrophic lateral sclerosis (ALS), epilepsy, schizophrenia, and hypoxic-ischemic brain injury. ROS can induce oxidative damage to lipids, nucleic acids, and proteins, promote abnormal aggregation of cytoskeletal proteins, inactivate major metabolic
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