Role of PGC-1 α in Mitochondrial Quality Control in Neurodegenerative Diseases.

Role of PGC-1α in Mitochondrial Quality Control in Neurodegenerative Diseases. Neurochem Res. 2019 Aug 13;: Authors: Zhang Q, Lei YH, Zhou JP, Hou YY, Wan Z, Wang HL, Meng H Abstract As one of the major cell organelles responsible for ATP production, it is important that neurons maintain mitochondria with structural and functional integrity; this is especially true for neurons with high metabolic requirements. When mitochondrial damage occurs, mitochondria are able to maintain a steady state of functioning through molecular and organellar quality control, thus ensuring neuronal function. And when mitochondrial quality control (MQC) fails, mitochondria mediate apoptosis. An apparently key molecule in MQC is the transcriptional coactivator peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α). Recent findings have demonstrated that upregulation of PGC-1α expression in neurons can modulate MQC to prevent mitochondrial dysfunction in certain in vivo and in vitro aging or neurodegenerative encephalopathy models, such as Huntington's disease, Alzheimer's disease, and Parkinson's disease. Because mitochondrial function and quality control disorders are the basis of pathogenesis in almost all neurodegenerative diseases (NDDs), the role of PGC-1α may make it a viable entry point for the treatment of such diseases. This review focuses on multi-level MQC in neurons, as well as the regulation of MQC by PGC-1α ...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research

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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
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Authors: Tabassum R, Jeong NY Abstract Oxidative phosphorylation is a source of energy production by which many cells satisfy their energy requirements. Endogenous reactive oxygen species (ROS) are by-products of oxidative phosphorylation. ROS are formed due to the inefficiency of oxidative phosphorylation, and lead to oxidative stress that affects mitochondrial metabolism. Chronic oxidative stress contributes to the onset of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The immediate consequences of oxidat...
Source: International Journal of Medical Sciences - Category: Biomedical Science Tags: Int J Med Sci Source Type: research
Publication date: Available online 31 October 2019Source: Molecular and Cellular NeuroscienceAuthor(s): Kevin McAvoy, Hibiki KawamataAbstractMitochondria play essential metabolic roles in neural cells. Mitochondrial dysfunction has profound effects on the brain. In primary mitochondrial diseases, mutations that impair specific oxidative phosphorylation (OXPHOS) proteins or OXPHOS assembly factors lead to isolated biochemical defects and a heterogeneous group of clinical phenotypes, including mitochondrial encephalopathies. A broader defect of OXPHOS function, due to mutations in proteins involved in mitochondrial DNA maint...
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research
Publication date: Available online 17 October 2019Source: Molecular Aspects of MedicineAuthor(s): J.V. Cabral-Costa, A.J. KowaltowskiAbstractThe brain is highly dependent on mitochondrial energy metabolism. As a result, mitochondrial dysfunction is a central aspect of many adult-onset neurological diseases, including stroke, ALS, Alzheimer's, Huntington's, and Parkinson's diseases. We review here how different mitochondrial functions, including oxidative phosphorylation, mitochondrial dynamics, oxidant generation, cell death regulation, Ca2+ homeostasis, and proteostasis are involved in these disorders.
Source: Molecular Aspects of Medicine - Category: Molecular Biology Source Type: research
Abstract NAD+ is a pivotal metabolite involved in cellular bioenergetics, genomic stability, mitochondrial homeostasis, adaptive stress responses, and cell survival. Multiple NAD+-dependent enzymes are involved in synaptic plasticity and neuronal stress resistance. Here, we review emerging findings that reveal key roles for NAD+ and related metabolites in the adaptation of neurons to a wide range of physiological stressors and in counteracting processes in neurodegenerative diseases, such as those occurring in Alzheimer's, Parkinson's, and Huntington diseases, and amyotrophic lateral sclerosis. Advances in underst...
Source: Cell Metabolism - Category: Cytology Authors: Tags: Cell Metab Source Type: research
Publication date: Available online 1 August 2019Source: Clinica Chimica ActaAuthor(s): Carmen Peña-Bautista, Máximo Vento, Miguel Baquero, Consuelo Cháfer-PericásAbstractNeurodegenerative diseases have great social and economic impact and cause millions of deaths every year. The potential molecular mechanisms in these pathologies have been widely studied and implicate lipid peroxidation as an important factor in the development of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. Data indicates that pathologic mechanisms specifically involve ferroptosis and ...
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research
-Pericás C Abstract Neurodegenerative diseases have great social and economic impact and cause millions of deaths every year. The potential molecular mechanisms in these pathologies have been widely studied and implicate lipid peroxidation as an important factor in the development of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. Data indicates that pathologic mechanisms specifically involve ferroptosis and mitochondrial dysfunction. Here we review the molecular mechanisms related to the lipid peroxidation that involve the development of neurodegeneration, as well as...
Source: International Journal of Clinical Chemistry - Category: Chemistry Authors: Tags: Clin Chim Acta Source Type: research
In this study we show, for the first time, significant alterations in cholesterol efflux capacity in adolescents throughout the range of BMI, a relationship between six circulating adipocyte-derived EVs microRNAs targeting ABCA1 and cholesterol efflux capacity, and in vitro alterations of cholesterol efflux in macrophages exposed to visceral adipose tissue adipocyte-derived EVs acquired from human subjects. These results suggest that adipocyte-derived EVs, and their microRNA content, may play a critical role in the early pathological development of ASCVD. Commentary on the Developing UK Government Position on Hea...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: Available online 6 July 2019Source: MitochondrionAuthor(s): Yuanbo Wu, Meiqiao Chen, Jielong JiangAbstractMitochondrial dysfunction is becoming one of the most emerging pathological process in the etiology of neurological disorders. Other common etiologies of the neurological disorders are aging and oxidative stress. Neurodegenerative disorders for instance Huntington's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Epilepsy, Schizophrenia, Multiple sclerosis, Neuropathic pain and Alzheimer's disease involves mitochondrial dysfunction and is regarded as the core of their pathological process...
Source: Mitochondrion - Category: Biochemistry Source Type: research
This study sought to investigate what could be learned from how these men have fared. The men were born in 1925-1928 and similar health-related data from questionnaires, physical examination, and blood samples are available for all surveys. Survival curves over various variable strata were applied to evaluate the impact of individual risk factors and combinations of risk factors on all-cause deaths. At the end of 2018, 118 (16.0%) of the men had reached 90 years of age. Smoking in 1974 was the strongest single risk factor associated with survival, with observed percentages of men reaching 90 years being 26.3, 25.7, ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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