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The CBS/H2S pathway in the brain

Title:  The CBS/H2S pathway in the brain
Investigator:  JJ Bruintjes
Promotor:  RH Henning, EA vd Zee
Summary:  Hibernating animals do not develop organ damage during their repetitive cycles of cooling-rewarming (torpor-arousal) and hence may serve as a paradigm for organ protection. This also applies to the brain, as hibernators show signs of brain damage, such as tau hyperfosforylation and loss of synaptic integrity, which is rapidly normalized after returning to euthermia. We previously coined the cystathionine beta synthase/hydrogen sulphide (CBS/H2S) pathway as an important protective mechanism. Moreover, pharmacological stimulation of the CBS/H2S pathway conveys protection from cooling/rewarming in cells. CBS expression is particularly high in brain, however its physiologic relevance is unknown. We hypothesize that the CBS/H2S pathway plays an important role in brain, due to its protective abilities. As such it may be involved in the pathogenesis of neurodegenerative diseases such as Alzheimer's Disease (AD). To this end we will analyze CBS expression in multiple animal species and in different conditions in the absence and presence of a blockade of CBS. Also, possible protective mechanisms of the CBS/H2S pathway will be explored in cultured neurons challenged with different types of damage. In these cells the CBS/H2S pathway will be modulated by genetic approaches and pharmacological compounds. Finally we will investigate the protective mechanisms of the CBS/H2S pathway in neurodegeneration by examining brains of transgenic Alzheimer's Disease (AD) mice and, if possible, human AD brains. 
Financing:  Junior Scientific Masterclass, MD/PhD bursary
Start:  1-04-2013
End:  1-04-2017 


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