title: CNB-001 a novel curcumin derivative, guards dopamine neurons in MPTP model of Parkinson's disease.
abstract: 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. This 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. These findings support the neuroprotective property of CNB-001 which may have strong therapeutic potential for treatment of PD.
authors.affiliation: Department of Biotechnology, Periyar University, Salem, Tamilnadu 636011, India.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Jayaraj
authors.affiliation: Department of Biotechnology, Periyar University, Salem, Tamilnadu 636011, India.
authors.forename: Namasivayam
authors.initials: N
authors.lastname: Elangovan
authors.affiliation: Department of Biotechnology, Periyar University, Salem, Tamilnadu 636011, India.
authors.forename: Krishnan
authors.identifier: 0000-0002-4998-4405
authors.initials: K
authors.lastname: Manigandan
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India.
authors.forename: Sonu
authors.initials: S
authors.lastname: Singh
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh 226031, India.
authors.forename: Shubha
authors.initials: S
authors.lastname: Shukla
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D059290:Dopaminergic Neurons / Q000187:drug effects; D005979:Glutathione Peroxidase; D006801:Humans; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology; D011720:Pyrazoles / Q000008:administration & dosage*
chemical_list: C529348:CNB 001; D018696:Neuroprotective Agents; D011720:Pyrazoles; D005979:Glutathione Peroxidase; D003474:Curcumin