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We are analyzing https://link.springer.com/article/10.1007/s12035-018-1118-5.

Title:
PARK14 (D331Y) PLA2G6 Causes Early-Onset Degeneration of Substantia Nigra Dopaminergic Neurons by Inducing Mitochondrial Dysfunction, ER Stress, Mitophagy Impairment and Transcriptional Dysregulation in a Knockin Mouse Model | Molecular Neurobiology
Description:
PARK14 patients with homozygous (D331Y) PLA2G6 mutation display motor deficits of pure early-onset Parkinson’s disease (PD). The aim of this study is to investigate the pathogenic mechanism of mutant (D331Y) PLA2G6-induced PD. We generated knockin (KI) mouse model of PARK14 harboring homozygous (D331Y) PLA2G6 mutation. Then, we investigated neuropathological and neurological phenotypes of PLA2G6D331Y/D331Y KI mice and molecular pathogenic mechanisms of (D331Y) PLA2G6-induced degeneration of substantia nigra (SN) dopaminergic neurons. Six-or nine-month-old PLA2G6D331Y/D331Y KI mice displayed early-onset cell death of SNpc dopaminergic neurons. Lewy body pathology was found in the SN of PLA2G6D331Y/D331Y mice. Six-or nine-month-old PLA2G6D331Y/D331Y KI mice exhibited early-onset parkinsonism phenotypes. Disrupted cristae of mitochondria were found in SNpc dopaminergic neurons of PLA2G6D331Y/D331Y mice. PLA2G6D331Y/D331Y mice displayed mitochondrial dysfunction and upregulated ROS production, which may lead to activation of apoptotic cascade. Upregulated protein levels of Grp78, IRE1, PERK, and CHOP, which are involved in activation of ER stress, were found in the SN of PLA2G6D331Y/D331Y mice. Protein expression of mitophagic proteins, including parkin and BNIP3, was downregulated in the SN of PLA2G6D331Y/D331Y mice, suggesting that (D331Y) PLA2G6 mutation causes mitophagy dysfunction. In the SN of PLA2G6D331Y/D331Y mice, mRNA levels of eight genes that are involved in neuroprotection/neurogenesis were decreased, while mRNA levels of two genes that promote apoptotic death were increased. Our results suggest that PARK14 (D331Y) PLA2G6 mutation causes degeneration of SNpc dopaminergic neurons by causing mitochondrial dysfunction, elevated ER stress, mitophagy impairment, and transcriptional abnormality.
Website Age:
28 years and 1 months (reg. 1997-05-29).

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Custom-built

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🌠 Phenomenal Traffic: 5M - 10M visitors per month


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Keywords {🔍}

pubmed, article, google, scholar, cas, central, parkinsons, disease, plag, mice, taiwan, chen, dopaminergic, neurons, chang, huang, wang, gung, taoyuan, mitochondrial, cell, neurosci, university, esm, plagdydy, brain, park, dysfunction, stress, chiu, yeh, cel, earlyonset, mitophagy, mouse, model, weng, mutation, parkinsonism, protein, phospholipase, medicine, hospital, degeneration, yingzu, lai, lin, hungli, access, knockout,

Topics {✒️}

wnt/beta-catenin signaling plays park14-linked young-onset parkinsonism month download article/chapter pure early-onset parkinson pla2g6d331y/d331y ki mice calcium-independent phospholipases a2 wnt/beta-catenin signaling xiap anti-caspase activity short-term synaptic plasticity national central university par-1/mark-tau axis tu-hsueh yeh ying-ling chen oxidative stress-induced phosphorylation angiotensin ii-induced transcriptional hung-li wang develops age-related neuropathology early-onset degeneration wen-hwa 1st road park14-dependent ca2+ signalling full article pdf calcium independent phospholipase szu-chia lai yin-cheng huang advanced molecular imaging yu-chuan liu lewy body pathology widespread lewy body arms/kidins220 scaffold protein chao-lang chen yi-chuan cheng yan-wei lin pla2g6d331y/d331y mice 18-mer peptide derived experimental animal center taiwan landseed hospital endoplasmic reticulum stress es cells microinjection kun-jun lin privacy choices/manage cookies ying-zu huang pla2g6 knockout mice article chiu app transgenic mice sumi-akamaru chia-chen hsu chang gung university age-mediated transcriptomic park14-linked parkinsonism yu-jie chen

Schema {🗺️}

WebPage:
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         headline:PARK14 (D331Y) PLA2G6 Causes Early-Onset Degeneration of Substantia Nigra Dopaminergic Neurons by Inducing Mitochondrial Dysfunction, ER Stress, Mitophagy Impairment and Transcriptional Dysregulation in a Knockin Mouse Model
         description:PARK14 patients with homozygous (D331Y) PLA2G6 mutation display motor deficits of pure early-onset Parkinson’s disease (PD). The aim of this study is to investigate the pathogenic mechanism of mutant (D331Y) PLA2G6-induced PD. We generated knockin (KI) mouse model of PARK14 harboring homozygous (D331Y) PLA2G6 mutation. Then, we investigated neuropathological and neurological phenotypes of PLA2G6D331Y/D331Y KI mice and molecular pathogenic mechanisms of (D331Y) PLA2G6-induced degeneration of substantia nigra (SN) dopaminergic neurons. Six-or nine-month-old PLA2G6D331Y/D331Y KI mice displayed early-onset cell death of SNpc dopaminergic neurons. Lewy body pathology was found in the SN of PLA2G6D331Y/D331Y mice. Six-or nine-month-old PLA2G6D331Y/D331Y KI mice exhibited early-onset parkinsonism phenotypes. Disrupted cristae of mitochondria were found in SNpc dopaminergic neurons of PLA2G6D331Y/D331Y mice. PLA2G6D331Y/D331Y mice displayed mitochondrial dysfunction and upregulated ROS production, which may lead to activation of apoptotic cascade. Upregulated protein levels of Grp78, IRE1, PERK, and CHOP, which are involved in activation of ER stress, were found in the SN of PLA2G6D331Y/D331Y mice. Protein expression of mitophagic proteins, including parkin and BNIP3, was downregulated in the SN of PLA2G6D331Y/D331Y mice, suggesting that (D331Y) PLA2G6 mutation causes mitophagy dysfunction. In the SN of PLA2G6D331Y/D331Y mice, mRNA levels of eight genes that are involved in neuroprotection/neurogenesis were decreased, while mRNA levels of two genes that promote apoptotic death were increased. Our results suggest that PARK14 (D331Y) PLA2G6 mutation causes degeneration of SNpc dopaminergic neurons by causing mitochondrial dysfunction, elevated ER stress, mitophagy impairment, and transcriptional abnormality.
         datePublished:2018-08-08T00:00:00Z
         dateModified:2018-08-08T00:00:00Z
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            Parkinson’s disease
            PARK14
            (D331Y) PLA2G6
            Knockin mice
            Neurosciences
            Neurobiology
            Cell Biology
            Neurology
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                        name:Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
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ScholarlyArticle:
      headline:PARK14 (D331Y) PLA2G6 Causes Early-Onset Degeneration of Substantia Nigra Dopaminergic Neurons by Inducing Mitochondrial Dysfunction, ER Stress, Mitophagy Impairment and Transcriptional Dysregulation in a Knockin Mouse Model
      description:PARK14 patients with homozygous (D331Y) PLA2G6 mutation display motor deficits of pure early-onset Parkinson’s disease (PD). The aim of this study is to investigate the pathogenic mechanism of mutant (D331Y) PLA2G6-induced PD. We generated knockin (KI) mouse model of PARK14 harboring homozygous (D331Y) PLA2G6 mutation. Then, we investigated neuropathological and neurological phenotypes of PLA2G6D331Y/D331Y KI mice and molecular pathogenic mechanisms of (D331Y) PLA2G6-induced degeneration of substantia nigra (SN) dopaminergic neurons. Six-or nine-month-old PLA2G6D331Y/D331Y KI mice displayed early-onset cell death of SNpc dopaminergic neurons. Lewy body pathology was found in the SN of PLA2G6D331Y/D331Y mice. Six-or nine-month-old PLA2G6D331Y/D331Y KI mice exhibited early-onset parkinsonism phenotypes. Disrupted cristae of mitochondria were found in SNpc dopaminergic neurons of PLA2G6D331Y/D331Y mice. PLA2G6D331Y/D331Y mice displayed mitochondrial dysfunction and upregulated ROS production, which may lead to activation of apoptotic cascade. Upregulated protein levels of Grp78, IRE1, PERK, and CHOP, which are involved in activation of ER stress, were found in the SN of PLA2G6D331Y/D331Y mice. Protein expression of mitophagic proteins, including parkin and BNIP3, was downregulated in the SN of PLA2G6D331Y/D331Y mice, suggesting that (D331Y) PLA2G6 mutation causes mitophagy dysfunction. In the SN of PLA2G6D331Y/D331Y mice, mRNA levels of eight genes that are involved in neuroprotection/neurogenesis were decreased, while mRNA levels of two genes that promote apoptotic death were increased. Our results suggest that PARK14 (D331Y) PLA2G6 mutation causes degeneration of SNpc dopaminergic neurons by causing mitochondrial dysfunction, elevated ER stress, mitophagy impairment, and transcriptional abnormality.
      datePublished:2018-08-08T00:00:00Z
      dateModified:2018-08-08T00:00:00Z
      pageStart:3835
      pageEnd:3853
      sameAs:https://doi.org/10.1007/s12035-018-1118-5
      keywords:
         Parkinson’s disease
         PARK14
         (D331Y) PLA2G6
         Knockin mice
         Neurosciences
         Neurobiology
         Cell Biology
         Neurology
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      author:
            name:Ching-Chi Chiu
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                  name:Chang Gung Memorial Hospital at Linkou
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                     name:Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
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               type:PostalAddress
            type:Organization
            name:Chang Gung University College of Medicine
            address:
               name:Healthy Aging Research Center, Chang Gung University College of Medicine, Taoyuan, Taiwan
               type:PostalAddress
            type:Organization
            name:Chang Gung Memorial Hospital at Linkou
            address:
               name:Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
               type:PostalAddress
            type:Organization
            name:Chang Gung University College of Medicine
            address:
               name:Department of Physiology and Pharmacology, Chang Gung University College of Medicine, Taoyuan, Taiwan
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan
      name:Healthy Aging Research Center, Chang Gung University College of Medicine, Taoyuan, Taiwan
      name:Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:Healthy Aging Research Center, Chang Gung University College of Medicine, Taoyuan, Taiwan
      name:Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:College of Medicine, Chang Gung University, Taoyuan, Taiwan
      name:Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:Healthy Aging Research Center, Chang Gung University College of Medicine, Taoyuan, Taiwan
      name:Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:College of Medicine, Chang Gung University, Taoyuan, Taiwan
      name:Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan
      name:Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:Healthy Aging Research Center, Chang Gung University College of Medicine, Taoyuan, Taiwan
      name:Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:College of Medicine, Chang Gung University, Taoyuan, Taiwan
      name:Institute of Cognitive Neuroscience, National Central University, Taoyuan, Taiwan
      name:Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:Healthy Aging Research Center, Chang Gung University College of Medicine, Taoyuan, Taiwan
      name:Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:College of Medicine, Chang Gung University, Taoyuan, Taiwan
      name:Graduate Institute of Biomedical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan
      name:College of Medicine, Chang Gung University, Taoyuan, Taiwan
      name:Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:Division of Sports Medicine, Taiwan Landseed Hospital, Taoyuan, Taiwan
      name:Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:Healthy Aging Research Center, Chang Gung University College of Medicine, Taoyuan, Taiwan
      name:Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:College of Medicine, Chang Gung University, Taoyuan, Taiwan
      name:Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:Molecular Imaging Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:Department of Neurology, Taipei Medical University Hospital, Taipei City, Taiwan
      name:School of Medicine, Taipei Medical University, Taipei, Taiwan
      name:Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:Healthy Aging Research Center, Chang Gung University College of Medicine, Taoyuan, Taiwan
      name:Division of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
      name:Department of Physiology and Pharmacology, Chang Gung University College of Medicine, Taoyuan, Taiwan
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