Mitochondrial dysfunction and oxidative stress in metabolic disorders — A step towards mitochondria based therapeutic strategies

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2016, Volume and Issue: 1863(5), P. 1066 - 1077

Published: Nov. 9, 2016

Language: Английский

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Mitochondrial dysfunction and oxidative stress in Parkinson's disease

Progress in Neurobiology, Journal Year: 2013, Volume and Issue: 106-107, P. 17 - 32

Published: April 30, 2013

Language: Английский

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Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease: implications for neuronal damage

Human Molecular Genetics, Journal Year: 2011, Volume and Issue: 20(13), P. 2495 - 2509

Published: March 31, 2011

The purpose of our study was to better understand the relationship between mitochondrial structural proteins, particularly dynamin-related protein 1 (Drp1) and amyloid beta (Aβ) in progression Alzheimer's disease (AD). Using qRT-PCR immunoblotting analyses, we measured mRNA levels genes frontal cortex patients with early, definite severe AD control subjects. We also characterized monomeric oligomeric forms Aβ these patients. immunoprecipitation/immunoblotting analysis, investigated interaction Drp1. immunofluorescence determined localization Drp1 intraneuronal brains primary hippocampal neurons from precursor (AβPP) transgenic mice. found increased expression fission Fis1 (fission 1) decreased fusion Mfn1 (mitofusin 1), Mfn2 2), Opa1 (optic atrophy Tomm40. matrix gene CypD up-regulated Results analyses suggest that abnormal dynamics increase as progresses. Immunofluorescence analysis antibody antibodies 6E10 A11 revealed colocalization Aβ. interacts monomers oligomers patients, interactions are progression. Primary were accumulated had lost branches degenerated, indicating may cause neuronal degeneration. These findings AD, production crucial factors fragmentation, synaptic damage. Inhibiting, be a therapeutic strategy reduce damage cognitive decline AD.

Language: Английский

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Mitochondrial Dysfunction in Neurodegenerative Diseases

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2012, Volume and Issue: 342(3), P. 619 - 630

Published: June 13, 2012

Neurodegenerative diseases are a large group of disabling disorders the nervous system, characterized by relative selective death neuronal subtypes. In most cases, there is overwhelming evidence impaired mitochondrial function as causative factor in these diseases. More recently, has emerged for dynamics (shape, size, fission-fusion, distribution, movement etc.) neurodegenerative such Parkinson9s disease, Huntington9s amyotrophic lateral sclerosis, and Alzheimer9s disease. Here, we provide concise overview major findings recent years highlighting importance healthy mitochondria neuron.

Language: Английский

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Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer's disease

Human Molecular Genetics, Journal Year: 2011, Volume and Issue: 20(23), P. 4515 - 4529

Published: Aug. 25, 2011

Increasing evidence suggests that the accumulation of amyloid beta (Aβ) in synapses and synaptic mitochondria causes mitochondrial failure degeneration Alzheimer's disease (AD). The purpose this study was to better understand effects Aβ activity alterations neurons from a mouse model AD. Using primary well-characterized precursor protein transgenic (AβPP) (Tg2576 line), for first time, we studied activity, including axonal transport mitochondria, dynamics, morphology function. Further, also nature Aβ-induced alterations, cell death Tg2576 mice, sought determine whether mitochondria-targeted antioxidant SS31 could mitigate oligomeric Aβ. We found significantly decreased anterograde movement, increased fission fusion, abnormal proteins defective function AβPP mice compared with wild-type (WT) neurons. Transmission electron microscopy revealed large number small structurally damaged broken cristae an apoptotic neuronal relative WT Our results intraneuronal Aβ, leading deficiencies, ultimately causing neurodegeneration cultures. However, restored viability, percentage indicating protects toxicity.

Language: Английский

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MAM (mitochondria-associated membranes) in mammalian cells: Lipids and beyond

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Journal Year: 2013, Volume and Issue: 1841(4), P. 595 - 609

Published: Dec. 6, 2013

Language: Английский

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Apoptosis and Oxidative Stress in Neurodegenerative Diseases

Journal of Alzheimer s Disease, Journal Year: 2014, Volume and Issue: 42(s3), P. S125 - S152

Published: Sept. 2, 2014

Neurodegenerative disorders affect almost 30 million individuals leading to disability and death. These are characterized by pathological changes in disease-specific areas of the brain degeneration distinct neuron subsets. Despite differences clinical manifestations neur onal vulnerability, processes appear similar, suggesting common neurodegenerative pathways. Apoptosis seems play a key role progression several neurologic like Alzheimer's disease, Parkinson's Huntington's amyotrophic lateral sclerosis as demonstrated studies on animal models cell lines. On other hand, research human brains reported contradictory results. However, many dying neurons have been detected patients with diseases, these conditions often associated significant loss accompanied typical morphological features apoptosis such chromatin condensation, DNA fragmentation, activation cysteine-proteases, caspases. Cell death linked oxidative stress imbalance between generation free radicals antioxidant defenses. Multiple sclerosis, stroke, diseases reactive oxygen species nitric oxide. Here we present an overview involvement neuronal most important mainly focusing attention genetic disorders, discussing interaction primary abnormalities apoptotic

Language: Английский

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Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration

Nature Neuroscience, Journal Year: 2019, Volume and Issue: 22(10), P. 1635 - 1648

Published: Sept. 23, 2019

Language: Английский

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Where the endoplasmic reticulum and the mitochondrion tie the knot: The mitochondria-associated membrane (MAM)

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2012, Volume and Issue: 1833(1), P. 213 - 224

Published: May 2, 2012

Language: Английский

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Novel Drp1 inhibitor diminishes aberrant mitochondrial fission and neurotoxicity

Journal of Cell Science, Journal Year: 2012, Volume and Issue: unknown

Published: Jan. 1, 2012

Excessive mitochondrial fission is associated with the pathology of a number neurodegenerative diseases. Therefore, inhibitors aberrant could provide important research tools as well potential leads for drug development. Using rational approach, we designed novel and selective peptide inhibitor, P110, excessive fission. P110 inhibits Drp1 enzyme activity blocks Drp1/Fis1 interaction in vitro cultured neurons whereas it has no effect on between other adaptors, demonstrated by co-immunoprecipitation. Further, using model Parkinson's disease (PD) culture, that neuroprotective inhibiting fragmentation ROS production subsequently improving membrane integrity. increased neuronal cell viability reducing apoptosis autophagic death, reduced neurite loss primary dopaminergic this PD culture model. We also found treatment appears to have minimal effects under basal conditions. Finally, required presence inhibit oxidative stress Together, our findings suggest inhibitor Drp1, might be useful diseases which dysfunction occur.

Language: Английский

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