Case 42502

Cabot, Richard C.; Castleman, Benjamin; Towne, Virginia W.

doi:10.1056/nejm195612132552411

Cited by 9 publications

(3 citation statements)

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“…This molecule also modifies the nuclear structure and the transcription process to trigger autophagy [ 28 , 29 ]. Moreover, mTOR regulates mitochondrial metabolism and promotes the translation of mitochondrial-bound proteins encoded in the nucleus, including mitochondrial transcription factor 1 (Tfam), cytochrome c oxidase (CoxI) subunit 1, and cytochrome c oxidase subunit IV mitochondrial (CoxIV) [ 29 , 30 ]. The activity of cytochrome C oxidase and of the respiratory chain is reduced in fibroblasts of patients with AFD [ 29 , 30 ].…”

Section: Mitochondrial Dysfunction In Anderson–fabry Diseasementioning

confidence: 99%

“…Moreover, mTOR regulates mitochondrial metabolism and promotes the translation of mitochondrial-bound proteins encoded in the nucleus, including mitochondrial transcription factor 1 (Tfam), cytochrome c oxidase (CoxI) subunit 1, and cytochrome c oxidase subunit IV mitochondrial (CoxIV) [ 29 , 30 ]. The activity of cytochrome C oxidase and of the respiratory chain is reduced in fibroblasts of patients with AFD [ 29 , 30 ]. Mitochondrial dysfunction, linked to the impairment of the mTOR pathway, has been evaluated by in vivo studies, which showed that the dysregulation of the autophagy–lysosomal pathway inhibits the mTOR-mediated control of mitochondrial metabolism in AFD cells [ 29 , 30 ].…”

Section: Mitochondrial Dysfunction In Anderson–fabry Diseasementioning

confidence: 99%

“…The activity of cytochrome C oxidase and of the respiratory chain is reduced in fibroblasts of patients with AFD [ 29 , 30 ]. Mitochondrial dysfunction, linked to the impairment of the mTOR pathway, has been evaluated by in vivo studies, which showed that the dysregulation of the autophagy–lysosomal pathway inhibits the mTOR-mediated control of mitochondrial metabolism in AFD cells [ 29 , 30 ].…”

Section: Mitochondrial Dysfunction In Anderson–fabry Diseasementioning

confidence: 99%

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Pathogenesis and Molecular Mechanisms of Anderson–Fabry Disease and Possible New Molecular Addressed Therapeutic Strategies

Tuttolomondo

Simonetta

Riolo

et al. 2021

IJMS

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Anderson–Fabry disease (AFD) is a rare disease with an incidenceof approximately 1:117,000 male births. Lysosomal accumulation of globotriaosylceramide (Gb3) is the element characterizing Fabry disease due to a hereditary deficiency α-galactosidase A (GLA) enzyme. The accumulation of Gb3 causes lysosomal dysfunction that compromises cell signaling pathways. Deposition of sphingolipids occurs in the autonomic nervous system, dorsal root ganglia, kidney epithelial cells, vascular system cells, and myocardial cells, resulting in organ failure. This manuscript will review the molecular pathogenetic pathways involved in Anderson–Fabry disease and in its organ damage. Some studies reported that inhibition of mitochondrial function and energy metabolism plays a significant role in AFD cardiomyopathy and in kidney disease of AFD patients. Furthermore, mitochondrial dysfunction has been reported as linked to the dysregulation of the autophagy–lysosomal pathway which inhibits the mechanistic target of rapamycin kinase (mTOR) mediated control of mitochondrial metabolism in AFD cells. Cerebrovascular complications due to AFD are caused by cerebral micro vessel stenosis. These are caused by wall thickening resulting from the intramural accumulation of glycolipids, luminal occlusion or thrombosis. Other pathogenetic mechanisms involved in organ damage linked to Gb3 accumulation are endocytosis and lysosomal degradation of endothelial calcium-activated intermediate-conductance potassium ion channel 3.1 (KCa3.1) via a clathrin-dependent process. This process represents a crucial event in endothelial dysfunction. Several studies have identified the deacylated form of Gb3, globotriaosylsphingosine (Lyso-Gb3), as the main catabolite that increases in plasma and urine in patients with AFD. The mean concentrations of Gb3 in all organs and plasma of Galactosidase A knockout mice were significantly higher than those of wild-type mice. The distributions of Gb3 isoforms vary from organ to organ. Various Gb3 isoforms were observed mainly in the kidneys, and kidney-specific Gb3 isoforms were hydroxylated. Furthermore, the action of Gb3 on the KCa3.1 channel suggests a possible contribution of this interaction to the Fabry disease process, as this channel is expressed in various cells, including endothelial cells, fibroblasts, smooth muscle cells in proliferation, microglia, and lymphocytes. These molecular pathways could be considered a potential therapeutic target to correct the enzyme in addition to the traditional enzyme replacement therapies (ERT) or drug chaperone therapy.

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Section: Mitochondrial Dysfunction In Anderson–fabry Diseasementioning

confidence: 99%

Section: Mitochondrial Dysfunction In Anderson–fabry Diseasementioning

confidence: 99%

Section: Mitochondrial Dysfunction In Anderson–fabry Diseasementioning

confidence: 99%

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Pathogenesis and Molecular Mechanisms of Anderson–Fabry Disease and Possible New Molecular Addressed Therapeutic Strategies

Tuttolomondo

Simonetta

Riolo

et al. 2021

IJMS

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Intramedullary cystic teratoma

et al. 1982

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Adult Intramedullary Mature Teratoma of the Spinal Cord: An Unusual Case with a Review of the Literature

Jeong,

Park,

Jun

2023

Nerve

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Intraspinal teratoma is a rare subtype of spinal cord tumors, accounting for only 0.2% to 0.5% of cases. These tumors consist of a mixture of two or more germ cell layers, including the ectoderm, endoderm, and mesoderm. They often contain epithelial tissues, fatty tissues, and follicles derived from these three layers, which can be visualized on magnetic resonance imaging (MRI) in most cases. However, in our patient, a 35-year-old woman with an intradural oval intramedullary teratoma at the L4 level, the tumor exhibited features similar to those of a schwannoma. On MRI, the tumor appeared as a 2-cm mass attached to the end of the spinal cord, with intermediate signal intensity on T2-weighted images and iso-intensity without enhancement on T1-weighted images. L4 laminoplasty with tumor removal was performed under intraoperative monitoring. The tumor was found to be firm with a cyst containing mucoid and fatty tissue posteriorly. Near-total resection was achieved, although the tumor margin was indistinct. A literature review revealed spinal cord tethering and the presence of fatty tissue without MRI enhancement as characteristic findings of teratomas and dermoid cysts.

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Case 42502

Cited by 9 publications

References 0 publications

Pathogenesis and Molecular Mechanisms of Anderson–Fabry Disease and Possible New Molecular Addressed Therapeutic Strategies

Pathogenesis and Molecular Mechanisms of Anderson–Fabry Disease and Possible New Molecular Addressed Therapeutic Strategies

Intramedullary cystic teratoma

Adult Intramedullary Mature Teratoma of the Spinal Cord: An Unusual Case with a Review of the Literature

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