Sirtuin mediated neuroprotection and its association with autophagy and apoptosis: Studies employing transgenic C. elegans model

Aamir Nazir,Pooja Jadiya

doi:10.1186/1750-1326-8-s1-p65

Abstract

Background Sirtuins, NAD+-dependent protein deacetylases, are well known for their role in longevity. Aging is the major known risk factor for the onset of Parkinson’s disease (PD). In our previous studies, SIRT1 induction by calorie restriction (CR) diet regimen has been shown to protect against dopaminergic neurodegeneration via sir-2.1 mediated pathway. Taking the studies forward, we endeavoured to understand the role of nicotinamide adenine dinucleotide activated protein deacetylase Sir2p/Sirt1 in calorie restriction mediated prevention of Parkinsonism employing transgenic Caenorhabditis elegans expressing human alpha synuclein.

Highlights

Sirtuins, NAD+-dependent protein deacetylases, are well known for their role in longevity
Gene silencing was achieved by employing RNAi methodology and the role of sirtuin was assayed by studying various parameters including alpha synuclein aggregation, content of reactive oxygen species, content of lipds, content of mitochondria and content of neurotransmitter dopamine
RNAi of sir-2.1 enhanced aggregation of alpha synuclein but sir-2.1 silenced worms raised on reduced calorie diet didn’t show protective effect in reducing protein aggregation which proved that protective effects of calorie restriction were mediated by NAD-dependent histone deacetylase activity of sir-2.1

Summary

Background

NAD+-dependent protein deacetylases, are well known for their role in longevity. Aging is the major known risk factor for the onset of Parkinson’s disease (PD). SIRT1 induction by calorie restriction (CR) diet regimen has been shown to protect against dopaminergic neurodegeneration via sir-2.1 mediated pathway. Taking the studies forward, we endeavoured to understand the role of nicotinamide adenine dinucleotide activated protein deacetylase Sir2p/Sirt in calorie restriction mediated prevention of Parkinsonism employing transgenic Caenorhabditis elegans expressing human alpha synuclein

Materials and methods

Results

Conclusions