title: Sir-2.1 modulates 'calorie-restriction-mediated' prevention of neurodegeneration in Caenorhabditis elegans: implications for Parkinson's disease.
abstract: The phenomenon of aging is known to modulate many disease conditions including neurodegenerative ailments like Parkinson's disease (PD) which is characterized by selective loss of dopaminergic neurons. Recent studies have reported on such effects, as calorie restriction, in modulating aging in living systems. We reason that PD, being an age-associated neurodegenerative disease might be modulated by interventions like calorie restriction. In the present study we employed the transgenic Caenorhabditis elegans model (P(dat-1)::GFP) expressing green fluorescence protein (GFP) specifically in eight dopaminergic (DA) neurons. Selective degeneration of dopaminergic neurons was induced by treatment of worms with 6-hydroxy dopamine (6-OHDA), a selective catecholaminergic neurotoxin, followed by studies on effect of calorie restriction on the neurodegeneration. Employing confocal microscopy of the dopaminergic neurons and HPLC analysis of dopamine levels in the nematodes, we found that calorie restriction has a preventive effect on dopaminergic neurodegeneration in the worm model. We further studied the role of sirtuin, sir-2.1, in modulating such an effect. Studies employing RNAi induced gene silencing of nematode sir-2.1, revealed that presence of Sir-2.1 is necessary for achieving the protective effect of calorie restriction on dopaminergic neurodegeneration. Our studies provide evidence that calorie restriction affords, an sir-2.1 mediated, protection against the dopaminergic neurodegeneration, that might have implications for neurodegenerative Parkinson's disease.
authors: Laboratory of Functional Genomics and Molecular Toxicology, Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow 226 001, UP, India.
authors: Pooja
authors: P
authors: Jadiya
authors: Manavi
authors: M
authors: Chatterjee
authors: Shreesh Raj
authors: SR
authors: Sammi
authors: Supinder
authors: S
authors: Kaur
authors: Gautam
authors: G
authors: Palit
authors: Aamir
authors: A
authors: Nazir
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D031204:Caloric Restriction; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000178:diet therapy* / Q000473:pathology; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D016627:Oxidopamine; C507014:SIR-2.1 protein, C elegans; D037761:Sirtuins; D004298:Dopamine