Dr Sarika Singh is currently Senior Scientist in the department of Toxicology & Experimental Medicine CSIR Central drug research institute India. she published more than 30 research articles. Her research interest is Diagnosis and therapeutics of neurodegenerative mechanisms is still mysterious field in comparison to other peripheral disease. The exploration of disease mechanisms in patients of neurological disease is immposible due to late diagnosis of disease and scarcity of peripheral biomarkers. In CNS also there are no biomarkers and physicians can only depend on the imaging like techniques for diagnosis. In this view we are exploring the disease mechanisms by using experimental disease models. Our main focus is on Parkinson’s disease and Alzheimer’s disease. We have reported that PD pathology involves the specific role of inducible nitric oxide synthase (NOS) in initiation of dopaminergic neuronal death (Singh et al, 2005). The involvement of mitochondria dependant energy metabolism and intrinsic apoptotic has also been reported during in neuronal death at early phase of disease pathology (Singh et al, 2010). Our both research articles were nationally and internationally cited by number of authors by more than 50 times. We have also reviewed the diversity and expressional regulation of NOS and apoptotic pathways involved in apoptotic death of dopaminergic neurons which are impressively cited by more than 100 authors to date (Kavya et al, 2007; Singh and Dikshit, 2007). Studies have suggested that pesticide rotenone could induce the Parkinson’s like pathology (mainly due to impaired mitochondrial activity) therefore, further my group focused on the investigation of subsequent neurodegenerative mechanisms. We have reported the rotenone and lipopolysacchride induced differential reponses in different rat brain regions. Study showed that the mid brain and striata regions of the rat brain are more vulnerable towards rotenone induced oxidative stress in comparison to other rat brain regions like frontal cortex and hippocampus (Swarnkar et al, 2010). Further we have studied the role of calcium and glia activation in rotenone induced neuronal death. The findings showed that rotenone caused brain region specific activation of astrocytes and microglia and death of neurons (Swarnkar et al, 2013). We have also reported that astrocytes activation is the key step in rotenone induced cytotoxicity and DNA damage (Swarnkar et al, 2012). Involvement of calcium homeostasis has also been reported in roteneon induced neuronal death (Swarnkar et al, 2012). Protein aggregation is also one of the hallmark of most of the neurodegenerative disease which could activate the unfolded protein responses (UPR). UPR involve the increased expression of chaperons and endoplasmic reticulum stress. In this direction we have reported the involvement of endoplasmic reticulam stress in rotenone induced neurotoxicity (Goswami et al, 2014). We have also reviewed the neuropathological responses of astrocytes and microglia under neurodegenerative conditions (Singh et al, 2011). We have reported the involvement of nitric oxide and mitochondria in neurotoxins 6-hydroxydopamine and lipopolysacchride induced DNA damage in astrocytes (Gupta et al, 2015). Further we are evaluating the disease related signaling mechanism involve in neuronal death.

 Diagnosis and therapeutics of neurodegenerative mechanisms is still mysterious field in comparison to other peripheral disease. The exploration of disease mechanisms in patients of neurological disease is immposible due to late diagnosis of disease and scarcity of peripheral biomarkers. In CNS also there are no biomarkers and physicians can only depend on the imaging like techniques for diagnosis. In this view we are exploring the disease mechanisms by using experimental disease models. Our main focus is on Parkinson’s disease and Alzheimer’s disease. We have reported that PD pathology involves the specific role of inducible nitric oxide synthase (NOS) in initiation of dopaminergic neuronal death (Singh et al, 2005). The involvement of mitochondria dependant energy metabolism and intrinsic apoptotic has also been reported during in neuronal death at early phase of disease pathology (Singh et al, 2010). Our both research articles were nationally and internationally cited by number of authors by more than 50 times. We have also reviewed the diversity and expressional regulation of NOS and apoptotic pathways involved in apoptotic death of dopaminergic neurons which are impressively cited by more than 100 authors to date (Kavya et al, 2007; Singh and Dikshit, 2007). Studies have suggested that pesticide rotenone could induce the Parkinson’s like pathology (mainly due to impaired mitochondrial activity) therefore, further my group focused on the investigation of subsequent neurodegenerative mechanisms. We have reported the rotenone and lipopolysacchride induced differential reponses in different rat brain regions. Study showed that the mid brain and striata regions of the rat brain are more vulnerable towards rotenone induced oxidative stress in comparison to other rat brain regions like frontal cortex and hippocampus (Swarnkar et al, 2010). Further we have studied the role of calcium and glia activation in rotenone induced neuronal death. The findings showed that rotenone caused brain region specific activation of astrocytes and microglia and death of neurons (Swarnkar et al, 2013). We have also reported that astrocytes activation is the key step in rotenone induced cytotoxicity and DNA damage (Swarnkar et al, 2012). Involvement of calcium homeostasis has also been reported in roteneon induced neuronal death (Swarnkar et al, 2012). Protein aggregation is also one of the hallmark of most of the neurodegenerative disease which could activate the unfolded protein responses (UPR). UPR involve the increased expression of chaperons and endoplasmic reticulum stress. In this direction we have reported the involvement of endoplasmic reticulam stress in rotenone induced neurotoxicity (Goswami et al, 2014). We have also reviewed the neuropathological responses of astrocytes and microglia under neurodegenerative conditions (Singh et al, 2011). We have reported the involvement of nitric oxide and mitochondria in neurotoxins 6-hydroxydopamine and lipopolysacchride induced DNA damage in astrocytes (Gupta et al, 2015). Further we are evaluating the disease related signaling mechanism involve in neuronal death.