title: Effect of pesticides on the aggregation of mutant huntingtin protein.
abstract: The classical reports on neurodegeneration concentrate on studying disruption of signalling cascades. Although it is now well recognized that misfolding and aggregation of specific proteins are associated with a majority of these diseases, their role in aggravating the symptoms is not so well understood. Huntington's disease (HD) is a neurodegenerative disorder that results from damage to complex II of mitochondria. In this work, we have studied the effect of mitochondrial complex I inhibitors, viz. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and rotenone, and complex II inhibitor, viz. 3-nitropropionic acid, on the aggregation of mutant huntingtin (mthtt) protein, whose misfolding and aggregation results in cellular abnormalities characteristic of HD. All three inhibitors were found to accelerate the aggregation of mthtt in vitro, although the amounts of aggregates formed were different in all cases. Thus, apart from their effect on mitochondrial viability, these neurotoxins are capable of interfering with the protein aggregation process and thus, hastening the onset of the disease.
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab, 160 062, India.
authors.forename: Ruhi S
authors.initials: RS
authors.lastname: Deshmukh
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Chaudhary
authors.forename: Ipsita
authors.initials: I
authors.lastname: Roy
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D050505:Mutant Proteins / Q000737:chemistry* / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000187:drug effects* / Q000302:isolation & purification; D009574:Nitro Compounds / Q000633:toxicity; D010575:Pesticides / Q000633:toxicity*; D011422:Propionates / Q000633:toxicity; D020836:Protein Structure, Quaternary; D012402:Rotenone / Q000633:toxicity
chemical_list: D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D009574:Nitro Compounds; D010575:Pesticides; D011422:Propionates; D012402:Rotenone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C015392:3-nitropropionic acid