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Her current research is focused on gaining a mechanistic understanding of abnormal sleep patterns and circadian rhythms in patients with neuropsychiatric and neurodegenerative disorders.She aims to identify traits in circadian and sleep rhythms that may be used as markers for the early detection of disorders in highrisk subjects and to develop therapeutic approaches for the Angelic Acid manipulation of circadian and sleep rhythms to improve the management of neuropsychiatric and neurodegenerative pathologies.She trained as a medicinal chemist and specialized in Venlafaxine hydrochloride pharmacology and neurochemistry, and she has actively contributed to research on cytokines and the control of hypothalamic temperature.More recently, she has contributed to the discovery of new histamine H antagonists and ligands for glutamate receptors.Her current focus is on neuropeptide receptor pharmacology and research into new approaches for the treatment of major depression and cognitive impairment.He has a longstanding interest in the application of behavioural methods to the study of central nervous system pharmacology.His focus is now on the mechanistic causes of neuropsychiatric illness and the methods that can be used to leverage this knowledge to provide better medicines for patients.His research spans the neurosciences, but is focused on two specific areas and these are the photobiology of vertebrate nonvisual photoreceptors his identification of inner retinal photoreceptors in the vertebrates is a key discovery in this area and circadian rhythm and sleep disruption in psychiatric and neurodegenerative disease.The mechanistic basis for this association between sleep disruption and neurodegenerative disease is providing insights into the neurobiology of sleep, circadian rhythms and mental health.View publication stats View publication stats In this review background is provided on the steadystate synthesis, regulation, and transport of glutathione, with primary focus on the brain.A brief overview is presented on the distinct but vital roles of glutathione in cellular maintenance and survival, and on the functions of key glutathionedependent enzymes.Major contributors to initiation and progression of neurodegenerative diseases are considered, including oxidative stress, protein misfolding, and protein aggregation.In each case examples of key regulatory mechanisms are identified that are sensitive to changes in glutathione redox status andor in the activities of glutathionedependent enzymes.Mechanisms of dysregulation of glutathione andor glutathionedependent enzymes are discussed that are implicated in pathogenesis of each neurodegenerative disease.Limitations in information or interpretation are identified, and possible avenues for further research are described with an aim to elucidating novel targets for therapeutic interventions.Multiple sclerosis ultimately leads to neurodegeneration, however it is primarily considered to be an autoimmune disease, so it is not discussed extensively herein.To provide perspective, the steadystate synthesis, regulation, and transport of GSH are described with emphasis on these processes in the brain.Then the functions of GSH as redox buffer, nucleophilic scavenger of electrophilic compounds, and signal transduction agent are presented.This corresponds approximately to a lower concentration than intracellular GSH levels.Thus intracellular synthesis is necessary for maintaining the large concentration difference.The enzymes involved in GSH synthesis are controlled by multiple mechanisms both prepost transcriptionally.For example, the human GCLC promoter contains multiple consensus sequences for transcription factors, including NFB, AP and antioxidant responseelectrophile response elements. Furthermore, regulation of GCS activity can be modulated via phosphorylation.

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