Research Article CNB-001 a Novel Curcumin Derivative, Guards Dopamine Neurons in MPTP Model of Parkinson’s Disease Richard L. Jayaraj, 1 Namasivayam Elangovan, 1 Krishnan Manigandan, 1 Sonu Singh, 2 and Shubha Shukla 2 1 Department of Biotechnology, Periyar University, Salem, Tamilnadu 636011, India 2 Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India Correspondence should be addressed to Namasivayam Elangovan; elangovannn@gmail.com Received 27 February 2014; Accepted 14 May 2014; Published 17 June 2014 Academic Editor: Arianna Scuteri Copyright © 2014 Richard L. Jayaraj et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Copious experimental and postmortem studies have shown that oxidative stress mediated degeneration of nigrostriatal dopaminergic neurons underlies Parkinson’s disease (PD) pathology. CNB-001, a novel pyrazole derivative of curcumin, has recently been reported to possess various neuroprotective properties. Tis study was designed to investigate the neuroprotective mechanism of CNB-001 in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rodent model of PD. Administration of MPTP (30 mg/kg for four consecutive days) exacerbated oxidative stress and motor impairment and reduced tyrosine hydroxylase (TH), dopamine transporter, and vesicular monoamine transporter 2 (VMAT2) expressions. Moreover, MPTP induced ultrastructural changes such as distorted cristae and mitochondrial enlargement in substantia nigra and striatum region. Pretreatment with CNB- 001 (24 mg/kg) not only ameliorated behavioral anomalies but also synergistically enhanced monoamine transporter expressions and cosseted mitochondria by virtue of its antioxidant action. Tese fndings support the neuroprotective property of CNB-001 which may have strong therapeutic potential for treatment of PD. 1. Introduction Parkinson’s disease (PD), a progressive neurodegenerative disorder, is characterized by degeneration of dopaminergic (DA-ergic) neurons in substantia nigra pars compacta (SNpc) and resultant loss of dopamine (DA) in the striatum (motor loci). Clinical diagnosis reports have shown that cardinal behavioral features of PD include rigidity, dyskinesia, gait imbalance, and tremor at rest [1]. Tough the etiology of PD remains obscure, various experimental studies have reported the involvement of oxidative stress, mitochondria dysfunction, apoptosis, and infammation either separately or cooperatively to induce neurodegeneration [2]. DA, a vital neurotransmitter (important for motor coordination), is synthesized in nigrostriatal pathway and undergoes autooxidation to form toxic reactive oxygen species (ROS) and quinone molecules which in turn initiates pathological response [3]. Apart from DA depletion, a profound reduction in specifc neurochemical markers such as tyrosine hydrolase (TH), DA transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) has been reported in PD [4, 5]. In idiopathic PD, mitochondrial complex I impairment leading to free radical generation which evokes respiratory chain defcits is very well documented [6]. Hence, various mitochondrial complex I inhibitors such as MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), rotenone, isoquinoline, paraquat, and 6-OHDA (6-hydroxydopamine) are used to create PD models to get insights into precise mechanisms underlying neurodegeneration in PD [7]. MPTP, a catecholamine neurotoxin, selectively degenerates dopaminergic neurons via monoamine oxidase-B- (MAO-B- ) mediated conversion of MPTP to its toxic/active metabolite MPP + . Further MPP + is taken into dopaminergic neurons via DA transporter and sequestered in mitochondria and inhibits complex I of electron transport chain resulting in enhanced ROS formation and decreased ATP production. Moreover, MPP + is also taken into the cytosol through vesicular monoamine transporter 2 (VMAT2) and supports lethality [8]. Hence, assessment of DAT and VMAT2 reveals a greater picture regarding DA integrity and Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 236182, 11 pages http://dx.doi.org/10.1155/2014/236182