Abnormal mitochondrial dynamics, mitochondrial loss and mutant huntingtin oligomers in Huntington's disease: implications for selective neuronal damage

Human Molecular Genetics, Journal Year: 2011, Volume and Issue: 20(7), P. 1438 - 1455

Published: Jan. 21, 2011

The purpose of our study was to determine the relationship between mutant huntingtin (Htt) and mitochondrial dynamics in progression Huntington's disease (HD). We measured mRNA levels electron transport chain genes, structural Drp1 (dynamin-related protein 1), Fis1 (fission Mfn1 (mitofusin Mfn2 2), Opa1 (optric atrophy Tomm40 (translocase outermembrane 40) CypD (cyclophilin D) grade III IV HD patients controls. Htt oligomers proteins were quantified striatum frontal cortex patients. Changes expressions genes found may represent a compensatory response damage caused by Htt. Increased expression decreased Mfn1, Mfn2, relative upregulated patients, this upregulation increased as progressed. Significantly immunoreactivity 8-hydroxy-guanosine cortical specimens from stage controls, suggesting oxidative DNA In contrast, significantly immunoreactivities cytochrome oxidase 1 b indicating loss function Immunoblotting analysis revealed 15, 25 50 kDa brain All oligomeric forms tissues nucleus mitochondria. increase Drp1, decrease be responsible for abnormal that we contribute neuronal presence neurons mitochondria disrupt functions. Based on these findings, propose association with imbalance impairs axonal mitochondria, decreases damages affected regions

Language: Английский

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Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer's disease: Implications to mitochondria-targeted antioxidant therapeutics

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2011, Volume and Issue: 1822(5), P. 639 - 649

Published: Oct. 21, 2011

Language: Английский

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Naturally occurring phytochemicals for the prevention of Alzheimer’s disease

Journal of Neurochemistry, Journal Year: 2009, Volume and Issue: 112(6), P. 1415 - 1430

Published: Dec. 26, 2009

Alzheimer's disease (AD) is an age-related neurodegenerative increasingly recognized as one of the most important medical problems affecting elderly. Although a number drugs, including several cholinesterase inhibitors and NMDA receptor antagonist, have been approved for use, they shown to produce diverse side effects yield relatively modest benefits. To overcome these limitations current therapeutics AD, extensive research development are underway identify drugs that effective free undesirable effects. Certain naturally occurring dietary polyphenolic phytochemicals received considerable recent attention alternative candidates AD therapy. In particular, curcumin, resveratrol, green tea catechins suggested potential prevent because their anti-amyloidogenic, anti-oxidative, anti-inflammatory properties. These also activate adaptive cellular stress responses, called 'neurohormesis', suppress processes. this commentary, we describe amyloid-beta-induced pathogenesis summarize intracellular molecular targets selected might slow progression AD.

Language: Английский

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Oxidative Stress Signaling in Alzheimers Disease

Current Alzheimer Research, Journal Year: 2008, Volume and Issue: 5(6), P. 525 - 532

Published: Dec. 1, 2008

Multiple lines of evidence demonstrate that oxidative stress is an early event in Alzheimers disease (AD), occurring prior to cytopathology, and therefore may play a key pathogenic role AD. Oxidative not only temporally precedes the pathological lesions but also activates cell signaling pathways, which, turn, contribute lesion formation and, at same time, provoke cellular responses such as compensatory upregulation antioxidant enzymes found vulnerable neurons In this review, we provide overview occur AD, particularly focused on potential sources roles mechanism activation stress-activated protein kinase pathways.

Language: Английский

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Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases

Brain Research Reviews, Journal Year: 2010, Volume and Issue: 67(1-2), P. 103 - 118

Published: Dec. 9, 2010

Language: Английский

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