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Title: Consequences of mitochondrial dysfunction in Huntington's Disease and protection via phosphorylation pathways
Authors: Cunha-Oliveira, Teresa 
Ferreira, Ildete L. 
Rego, A. Cristina 
Keywords: Huntington's Disease
Issue Date: Feb-2012
Publisher: InTech- Open Access Publisher
Serial title, monograph or event: Huntington’s Disease - Core Concepts and Current Advances
Abstract: Huntington’s Disease (HD) is an autosomal dominant neurodegenerative disorder clinically characterized by psychiatric disturbances, progressive cognitive impairment and choreiform movements. These symptoms are associated with the selective atrophy and neuronal loss in the striatum, cortex and hypothalamus. The disease is caused by a mutation at the 5’ terminal of the huntingtin (HTT) gene involving the expansion of CAG triplet, which encodes for glutamine. Mutant huntingtin (mHtt) may be cleaved by proteases originating neurotoxic fragments, and also undergoes conformational changes that lead to the formation of protein aggregates (Gil and Rego 2008, for review). Among several mechanisms of neurodegeneration, mHtt is related to mitochondrial dysfunction and relevant changes in energy metabolism in both central and peripheral cells, which may underlie cell death (Gil and Rego 2008, for review). In this review chapter we emphasize the role of mitochondrial dysfunction in neurodegeneration in HD, particularly centering on loss of mitochondrial activity and the regulation of intrinsic apoptosis in central and peripheral HD human tissue or cells, and in animal models of HD. We focus on the changes in energy metabolism, oxidative stress, the link to transcriptional dysfunction and the regulation of intrinsic apoptosis. We further explore the therapeutic role of promoting phosphorylation pathways through selective inhibition of phosphatases (e.g. with FK506) and/or activation of kinase signaling cascades mediated by neurotrophins, namely brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF).
ISBN: 979-953-307-066-6
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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