Lipids and lipoxidation in human brain aging. Mitochondrial ATP-synthase as a key lipoxidation target

Jové, Mariona; Pradas, Irene; Dominguez-Gonzalez, Mayelin; Ferrer, Isidro; Pamplona, Reinald

doi:10.1016/j.redox.2018.101082

Cited by 56 publications

(49 citation statements)

References 109 publications

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“…Several anti-oxidative factors such as glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) regulate the levels of ROS that are mainly generated by the mitochondrial respiratory chain [28][29][30][31]. In the cytosol, enzymes such as amino acid oxidases, cyclooxygenases, lipoxygenases, nitric oxide (NO) synthase, and xanthine oxidase also generate ROS such as superoxide anions, peroxides and others [32][33][34].…”

Section: Oxidative Stressmentioning

confidence: 99%

Role of mitochondrial quality control in the pathogenesis of nonalcoholic fatty liver disease

Toan

Zhou

2020

Aging

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Nutrient oversupply and mitochondrial dysfunction play central roles in nonalcoholic fatty liver disease (NAFLD). The mitochondria are the major sites of β-oxidation, a catabolic process by which fatty acids are broken down. The mitochondrial quality control (MQC) system includes mitochondrial fission, fusion, mitophagy and mitochondrial redox regulation, and is essential for the maintenance of the functionality and structural integrity of the mitochondria. Excessive and uncontrolled production of reactive oxygen species (ROS) in the mitochondria damages mitochondrial components, including membranes, proteins and mitochondrial DNA (mtDNA), and triggers the mitochondrial pathway of apoptosis. The functionality of some damaged mitochondria can be restored by fusion with normally functioning mitochondria, but when severely damaged, mitochondria are segregated from the remaining functional mitochondrial network through fission and are eventually degraded via mitochondrial autophagy, also called as mitophagy. In this review, we describe the functions and mechanisms of mitochondrial fission, fusion, oxidative stress and mitophagy in the development and progression of NAFLD.

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Section: Oxidative Stressmentioning

confidence: 99%

Role of mitochondrial quality control in the pathogenesis of nonalcoholic fatty liver disease

Toan

Zhou

2020

Aging

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“…Furthermore, it underscores the impact of neural dysfunction in the loss of smell at aging, beyond the changes occurring in the olfactory epithelium over time. In P. leucopus, processes associated with lipid metabolism were suggested that may reflect adaptive responses due to the aging-associated loss of lipid content in the brain [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Resilience, plasticity and robustness in gene expression during aging in the brain of outbred deer mice

et al. 2021

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Background Genes that belong to the same network are frequently co-expressed, but collectively, how the coordination of the whole transcriptome is perturbed during aging remains unclear. To explore this, we calculated the correlation of each gene in the transcriptome with every other, in the brain of young and older outbred deer mice (P. leucopus and P. maniculatus). Results In about 25 % of the genes, coordination was inversed during aging. Gene Ontology analysis in both species, for the genes that exhibited inverse transcriptomic coordination during aging pointed to alterations in the perception of smell, a known impairment occurring during aging. In P. leucopus, alterations in genes related to cholesterol metabolism were also identified. Among the genes that exhibited the most pronounced inversion in their coordination profiles during aging was THBS4, that encodes for thrombospondin-4, a protein that was recently identified as rejuvenation factor in mice. Relatively to its breadth, abolishment of coordination was more prominent in the long-living P. leucopus than in P. maniculatus but in the latter, the intensity of de-coordination was higher. Conclusions There sults suggest that aging is associated with more stringent retention of expression profiles for some genes and more abrupt changes in others, while more subtle but widespread changes in gene expression appear protective. Our findings shed light in the mode of the transcriptional changes occurring in the brain during aging and suggest that strategies aiming to broader but more modest changes in gene expression may be preferrable to correct aging-associated deregulation in gene expression.

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“…Phospholipids are structurally and functionally important cell membrane constituents. Numerous studies have been conducted to examine their role in aging [ 40 ], as phospholipids are the primary functional components of neuronal membranes [ 41 ]. These results suggest that PLDP represents a promising nutraceutical that could improve cognitive function in healthy adults over 40 years of age.…”

Section: Pldp and Cognitive Improvementmentioning

confidence: 99%

Therapeutic Potential of Porcine Liver Decomposition Product: New Insights and Perspectives for Microglia-Mediated Neuroinflammation in Neurodegenerative Diseases

et al. 2020

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It is widely accepted that microglia-mediated inflammation contributes to the progression of neurodegenerative diseases; however, the precise mechanisms through which these cells contribute remain to be elucidated. Microglia, as the primary immune effector cells of the brain, play key roles in maintaining central nervous system (CNS) homeostasis. Microglia are located throughout the brain and spinal cord and may account for up to 15% of all cells in the brain. Activated microglia express pro-inflammatory cytokines that act on the surrounding brain and spinal cord. Microglia may also play a detrimental effect on nerve cells when they gain a chronic inflammatory function and promote neuropathologies. A key feature of microglia is its rapid morphological change upon activation, characterized by the retraction of numerous fine processes and the gradual acquisition of amoeba-like shapes. These morphological changes are also accompanied by the expression and secretion of inflammatory molecules, including cytokines, chemokines, and lipid mediators that promote systemic inflammation during neurodegeneration. This may be considered a protective response intended to limit further injury and initiate repair processes. We previously reported that porcine liver decomposition product (PLDP) induces a significant increase in the Hasegawa’s Dementia Scale-Revised (HDS-R) score and the Wechsler Memory Scale (WMS) in a randomized, double-blind, placebo-controlled study in healthy humans. In addition, the oral administration of porcine liver decomposition product enhanced visual memory and delayed recall in healthy adults. We believe that PLDP is a functional food that aids cognitive function. In this review, we provide a critical assessment of recent reports of lysophospholipids derived from PLDP, a rich source of phospholipids. We also highlight some recent findings regarding bidirectional interactions between lysophospholipids and microglia and age-related neurodegenerative diseases such as dementia and Alzheimer’s disease.

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Lipids and lipoxidation in human brain aging. Mitochondrial ATP-synthase as a key lipoxidation target

Cited by 56 publications

References 109 publications

Role of mitochondrial quality control in the pathogenesis of nonalcoholic fatty liver disease

Role of mitochondrial quality control in the pathogenesis of nonalcoholic fatty liver disease

Resilience, plasticity and robustness in gene expression during aging in the brain of outbred deer mice

Therapeutic Potential of Porcine Liver Decomposition Product: New Insights and Perspectives for Microglia-Mediated Neuroinflammation in Neurodegenerative Diseases

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