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Reticular stress in the Alzheimer's disease : role of the XBP-1s transcription factor

Thesis

French

ID: <10670/1.wb7evd>

Abstract

Alzheimer's disease is a neurodegenerative pathology strongly correlated to aging. Its symptoms are characterized by an impaired short term memory process in the early stages of the disease and later on by a loss of all type of memory process. There is actually no cure for this pathology. At the histo-pathological levels, the disease show an accumulation of aggregated proteins in the brain (called amyloid protein) in the intra or extra cellular space, which act as a disruptor of the normal neuronal function and activity. Thus, most of the therapeutic approach to treat the disease aim at removing those proteins aggregates from the brain. However, some of the Alzheimer's disease characteristics could be melded with normal aging : One such case is the global decrease of the proteostasis mechanism in the cell which normally happen in normal brain. The assumption made during this work is that the recovery of these mechanisms impaired by age would constitute a credible therapeutic approach, complementary to the other existing approaches to the complex disease that is Alzheimer's disease. Following this hypothesis I was interested in the role and regulation of one of the major system controlling proteostasis: the UPR (unfolded protein response), and particulary to the XBP-1s transcription factor , considered one of the master regulator of this cellular network

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