Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To address mitochondrial dysfunction that mediates irreversible visual loss and neurodegeneration of the optic nerve in the experimental autoimmune encephalomyelitis (EAE) animal model of multiple sclerosis (MS), mice sensitized for EAE were vitreally injected with self-complementary adenoassociated virus (scAAV) containing the NADH-dehydrogenase type-2 (NDI1) complex I gene that quickly expressed in mitochondria of almost all retinal ganglion cells (RGCs). Visual function assessed by pattern electroretinograms (PERGs) reduced by half in EAE showed no significant reductions with NDI1. Serial optical coherence tomography (OCT) revealed significant inner retinal thinning with EAE that was suppressed by NDI1. Although complex I activity reduced 80% in EAE was not improved by NDI1, in vivo fluorescent probes indicated mitochondrial oxidative stress and apoptosis of the EAE retina were reduced by NDI1. Finally, the 42% loss of axons in the EAE optic nerve was ameliorated by NDI1. Targeting the dysfunctional complex I of EAE responsible for loss of respiration, mitochondrial oxidative stress and apoptosis may be a novel approach to address neuronal and axonal loss responsible for permanent disability that is unaltered by current disease modifying drugs for MS that target inflammation.
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PMID:NADH-dehydrogenase type-2 suppresses irreversible visual loss and neurodegeneration in the EAE animal model of MS. 2375 9

Mitochondrial dysfunction mediated loss of respiration, oxidative stress, and loss of cellular homeostasis contributes to the neuronal and axonal degenerations permanent loss of function in experimental autoimmune encephalomyelitis model (EAE) of multiple sclerosis (MS). To address the mitochondrial dysfunction mediated visual loss in EAE mice, self-complementary adeno-associated virus (scAAV) containing the NADH-dehydrogenase type-2 (NDI1) complex I gene was intravitreally injected into the mice after the onset of visual defects. Visual function assessed by pattern electroretinogram (PERGs) showed progressive loss of function in EAE mice were improved significantly in NDI1 gene therapy-treated mice. Serial optical coherence tomography (OCT) revealed that progressive thinning of inner retinal layers in EAE mice was prevented upon NDI1 expression. The 45% optic nerve axonal and 33% retinal ganglion cell (RGC) loss contributed to the permanent loss of visual function in EAE mice were ameliorated by NDI1-mediated prevention of mitochondrial cristae dissolution and improved mitochondrial homeostasis. In conclusion, targeting the dysfunctional complex I using NDI1 gene can be an approach to address axonal and neuronal loss responsible for permanent disability in MS that is unaltered by current disease modifying drugs.
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PMID:Gene Therapy with Single-Subunit Yeast NADH-Ubiquinone Oxidoreductase (NDI1) Improves the Visual Function in Experimental Autoimmune Encephalomyelitis (EAE) Mice Model of Multiple Sclerosis (MS). 3190 Aug 64

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a recently described autosomal dominant disorder caused by mutations in the nuclear receptor subfamily 2 group F member 1 (NR2F1) gene. Its common features include optic atrophy and/or hypoplasia, developmental delay, intellectual disability, attention deficit disorder, autism spectrum disorder, seizures, hearing defects, spasticity, hypotonia, and thinning of the corpus callosum. Mitochondrial involvement has also been described with BBSOAS. Currently, 31 cases of BBSOAS have been described in the literature. Here we report a case of undiagnosed BBSOAS presenting as psychosis in a 32-year-old man with a history of bilateral optic nerve atrophy, intellectual disability, epilepsy, and mitochondrial complex I abnormality on muscle biopsy. Whole-genome sequencing identified a heterozygous de novo nonsense mutation in the NR2F1 gene [c.253 G>T (guanine to thymine mutation in coding position 253) in exon 1, p.E85X variant (GAG>TAG) (glutamic acid to stop codon mutation; protein truncated to 85 amino acids)]. A pathogenic nonsense mutation has not previously been reported in the literature in association with BBSOAS and represents an expansion of clinically relevant variants. Psychosis has also not been previously reported in this syndrome and may represent a phenotypic expansion of BBSOAS, a manifestation of prolonged disease, or a result of disease management.
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PMID:Bosch-Boonstra-Schaaf Optic Atrophy Syndrome Presenting as New-Onset Psychosis in a 32-Year-Old Man: A Case Report and Literature Review. 3191 71

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a recently described autosomal dominant disorder caused by mutations in the nuclear receptor subfamily 2 group F member 1 (NR2F1) gene. Its common features include optic atrophy and/or hypoplasia, developmental delay, intellectual disability, attention deficit disorder, autism spectrum disorder, seizures, hearing defects, spasticity, hypotonia, and thinning of the corpus callosum. Mitochondrial involvement has also been described with BBSOAS. Currently, 31 cases of BBSOAS have been described in the literature. Here we report a case of undiagnosed BBSOAS presenting as psychosis in a 32-year-old man with a history of bilateral optic nerve atrophy, intellectual disability, epilepsy, and mitochondrial complex I abnormality on muscle biopsy. Whole-genome sequencing identified a heterozygous de novo nonsense mutation in the NR2F1 gene [c.253 G>T (guanine to thymine mutation in coding position 253) in exon 1, p.E85X variant (GAG>TAG) (glutamic acid to stop codon mutation; protein truncated to 85 amino acids)]. A pathogenic nonsense mutation has not previously been reported in the literature in association with BBSOAS and represents an expansion of clinically relevant variants. Psychosis has also not been previously reported in this syndrome and may represent a phenotypic expansion of BBSOAS, a manifestation of prolonged disease, or a result of disease management.
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PMID:Commentary on "Bosch-Boonstra-Schaaf Optic Atrophy Syndrome Presenting as New-Onset Psychosis in a 32-Year-Old Man: A Case Report and Literature Review". 3191 72