Peroxisome quality control and dysregulated lipid metabolism in neurodegenerative diseases

Jo, Doo Sin; Park, Na Yeon; Cho, Dong‐Hyung

doi:10.1038/s12276-020-00503-9

Cited by 65 publications

(54 citation statements)

References 132 publications

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“…The interaction between MLYCD and HSD17B4 influences fatty acid oxidation. Additionally, MLYCD and HSD17B4 , which play an important role in mitochondrial function, lipid metabolism, and endothelial structure, are expressed in the cerebral artery and adipose tissue ( Gautier et al, 2015 ; Chaanine et al, 2019 ; Jo et al, 2020 ). The PRKCD – LYZ2 pair is reported to be strongly correlated with the inflammation response ( Xu et al, 2014 ) and may promote the activation of chronic systemic inflammation.…”

Section: Resultsmentioning

confidence: 99%

Multiple-Tissue and Multilevel Analysis on Differentially Expressed Genes and Differentially Correlated Gene Pairs for HFpEF

et al. 2021

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Heart failure with preserved ejection fraction (HFpEF) is a complex disease characterized by dysfunctions in the heart, adipose tissue, and cerebral arteries. The elucidation of the interactions between these three tissues in HFpEF will improve our understanding of the mechanism of HFpEF. In this study, we propose a multilevel comparative framework based on differentially expressed genes (DEGs) and differentially correlated gene pairs (DCGs) to investigate the shared and unique pathological features among the three tissues in HFpEF. At the network level, functional enrichment analysis revealed that the networks of the heart, adipose tissue, and cerebral arteries were enriched in the cell cycle and immune response. The networks of the heart and adipose tissues were enriched in hemostasis, G-protein coupled receptor (GPCR) ligand, and cancer-related pathway. The heart-specific networks were enriched in the inflammatory response and cardiac hypertrophy, while the adipose-tissue-specific networks were enriched in the response to peptides and regulation of cell adhesion. The cerebral-artery-specific networks were enriched in gene expression (transcription). At the module and gene levels, 5 housekeeping DEGs, 2 housekeeping DCGs, 6 modules of merged protein–protein interaction network, 5 tissue-specific hub genes, and 20 shared hub genes were identified through comparative analysis of tissue pairs. Furthermore, the therapeutic drugs for HFpEF-targeting these genes were examined using molecular docking. The combination of multitissue and multilevel comparative frameworks is a potential strategy for the discovery of effective therapy and personalized medicine for HFpEF.

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Section: Resultsmentioning

confidence: 99%

Multiple-Tissue and Multilevel Analysis on Differentially Expressed Genes and Differentially Correlated Gene Pairs for HFpEF

et al. 2021

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“…The severity of these alternations correlates with the progression of disease [ 402 , 403 ] and has been shown to change cell membrane properties and increase intracellular cholesterol levels. These changes increase β-secretase and γ-secretase activities, resulting in enhanced Aβ generation, tau hyperphosphorylation, synaptic dysfunction, and neuroinflammation [ 404 , 405 ]. In addition, peroxisomal β-oxidation inhibition increased Aβ generation in rat brains (reviewed in [ 405 ]).…”

Section: Molecular Mechanisms Of Altered Metabolism In Nddsmentioning

confidence: 99%

“…These changes increase β-secretase and γ-secretase activities, resulting in enhanced Aβ generation, tau hyperphosphorylation, synaptic dysfunction, and neuroinflammation [ 404 , 405 ]. In addition, peroxisomal β-oxidation inhibition increased Aβ generation in rat brains (reviewed in [ 405 ]). Similarly, severe alterations in lipid composition (reductions in DHA and plasmalogens) of frontal cortex lipid rafts from PD patients have been reported [ 406 ].…”

Section: Molecular Mechanisms Of Altered Metabolism In Nddsmentioning

confidence: 99%

“…Further studies are required to determine whether peroxisomal lipid dysfunction directly contributes to disease etiology or is a secondary phenomenon. We refer the reader to another recent review for a detailed overview of the peroxisomal lipid metabolism in NDDs and its metabolic cooperation with mitochondria [ 405 , 408 ].…”

Section: Molecular Mechanisms Of Altered Metabolism In Nddsmentioning

confidence: 99%

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Reappraisal of metabolic dysfunction in neurodegeneration: Focus on mitochondrial function and calcium signaling

Jadiya

Garbincius

Elrod

2021

acta neuropathol commun

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The cellular and molecular mechanisms that drive neurodegeneration remain poorly defined. Recent clinical trial failures, difficult diagnosis, uncertain etiology, and lack of curative therapies prompted us to re-examine other hypotheses of neurodegenerative pathogenesis. Recent reports establish that mitochondrial and calcium dysregulation occur early in many neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson’s disease, Huntington's disease, and others. However, causal molecular evidence of mitochondrial and metabolic contributions to pathogenesis remains insufficient. Here we summarize the data supporting the hypothesis that mitochondrial and metabolic dysfunction result from diverse etiologies of neuropathology. We provide a current and comprehensive review of the literature and interpret that defective mitochondrial metabolism is upstream and primary to protein aggregation and other dogmatic hypotheses of NDDs. Finally, we identify gaps in knowledge and propose therapeutic modulation of mCa2+ exchange and mitochondrial function to alleviate metabolic impairments and treat NDDs.

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“…The β-oxidation of short-, medium-, and long-chain fatty acids predominantly occurs in the mitochondria under physiological conditions. Peroxisomal dysfunction is related to neurodegenerative diseases and brain aging [ 108 , 109 ]. Perturbation of fatty acid composition in the brain is one of the triggers of neurodegenerative disease.…”

Section: Alternation Of Organelle Function Regarding Lipid Peroxidation and Protein Aggregationmentioning

confidence: 99%

Cell Death via Lipid Peroxidation and Protein Aggregation Diseases

Iuchi

Takai

Higuchi

2021

Biology

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Lipid peroxidation of cellular membranes is a complicated cellular event, and it is both the cause and result of various diseases, such as ischemia-reperfusion injury, neurodegenerative diseases, and atherosclerosis. Lipid peroxidation causes non-apoptotic cell death, which is associated with cell fate determination: survival or cell death. During the radical chain reaction of lipid peroxidation, various oxidized lipid products accumulate in cells, followed by organelle dysfunction and the induction of non-apoptotic cell death. Highly reactive oxidized products from unsaturated fatty acids are detected under pathological conditions. Pathological protein aggregation is the general cause of these diseases. The cellular response to misfolded proteins is well-known as the unfolded protein response (UPR) and it is partially concomitant with the response to lipid peroxidation. Moreover, the association between protein aggregation and non-apoptotic cell death by lipid peroxidation is attracting attention. The link between lipid peroxidation and protein aggregation is a matter of concern in biomedical fields. Here, we focus on lethal protein aggregation in non-apoptotic cell death via lipid peroxidation. We reviewed the roles of protein aggregation in the initiation and execution of non-apoptotic cell death. We also considered the relationship between protein aggregation and oxidized lipid production. We provide an overview of non-apoptotic cell death with a focus on lipid peroxidation for therapeutic targeting during protein aggregation diseases.

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Peroxisome quality control and dysregulated lipid metabolism in neurodegenerative diseases

Cited by 65 publications

References 132 publications

Multiple-Tissue and Multilevel Analysis on Differentially Expressed Genes and Differentially Correlated Gene Pairs for HFpEF

Multiple-Tissue and Multilevel Analysis on Differentially Expressed Genes and Differentially Correlated Gene Pairs for HFpEF

Reappraisal of metabolic dysfunction in neurodegeneration: Focus on mitochondrial function and calcium signaling

Cell Death via Lipid Peroxidation and Protein Aggregation Diseases

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