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Neurodegenerative mechanisms in Alzheimer's disease : amyloid aggregation, neuroinflammation and apoptosis

By Ivica Granic

Abstract

In this thesis several new therapeutic strategies were developed and evaluated in the prevention of Alzheimer's disease. The pathology of Alzheimer's disease consists of neuronal inflammation, death of nerve cells caused among others by the accumulation and aggregation of the amyloid-beta protein. This eventually leads to the decay of the brain which is associated with symptoms such as general cognitive decline, memory loss and personality changes. A major problem in many neurodegenerative diseases is the neuronal cell death by overstimulation of the neuronal cells induced by Aβ or glutamate. Interestingly the cholesterol-lowering drug "Lovastatin" provides protection against this kind of cell death. The same effect is seen after calpain inhibition or treatment with TNF-α. A novel peptide is designed and synthesized using a computer simulation. This peptide protected cells against Aβ-induced cell death. With these different treatments cognitive decline was prevented without disturbing physiological neuronal functions. These studies demonstrated that various mechanisms have the potential to intervene in Alzheimer pathology. However, it is still unclear what type of treatment is the best approach in patients because these results were obtained from cell cultures and animal models. Moreover, the question remains whether these drugs will be able to prevent or stop all aspects of this complex disease. From this perspective one can speculate whether it is necessary to intervene on multiple molecular processes for an effective treatment in Alzheimer Disease.

Topics: Cholesterol, Ontstekingen (geneeskunde),; Celdood; Tumor necrosis factor; Amyloïd; Nucleus basalis; Ziekte van Alzheimer; Zenuwstelselaandoeningen; Proefschriften (vorm); geriatrie; gerontologie
Year: 2010
OAI identifier: oai:ub.rug.nl:dbi/4c0f3b8a9d5da
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