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Article ; Online: Exploring the Mechanism of Activation of CFTR by Curcuminoids: An Ensemble Docking Study.

Bellacchio, Emanuele

International journal of molecular sciences

2023 Volume 25, Issue 1

Abstract: Curcumin, a major constituent of turmeric ( ...

Abstract	Curcumin, a major constituent of turmeric (
MeSH term(s)	Humans ; Diarylheptanoids ; Curcumin/pharmacology ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Cystic Fibrosis ; Nucleotides ; Adenosine Triphosphate
Chemical Substances	Diarylheptanoids ; Curcumin (IT942ZTH98) ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; Nucleotides ; Adenosine Triphosphate (8L70Q75FXE) ; CFTR protein, human
Language	English
Publishing date	2023-12-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25010552
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Article ; Online: Intramolecular Interaction with the E6 Region Stabilizes the Closed Conformation of the N-SH2 Domain and Concurs with the Self-Inhibitory Docking in Downregulating the Activity of the SHP2 Tyrosine Phosphatase: A Molecular Dynamics Study.

Bellacchio, Emanuele

International journal of molecular sciences

2022 Volume 23, Issue 9

Abstract: The localization and activity of the SHP2 tyrosine phosphatase across different cellular compartments to the target substrates are steered by the binding of phosphotyrosine (pY) peptides to the tandem SH2 domains. The most N-terminal domain (N-SH2) can ... ...

Abstract	The localization and activity of the SHP2 tyrosine phosphatase across different cellular compartments to the target substrates are steered by the binding of phosphotyrosine (pY) peptides to the tandem SH2 domains. The most N-terminal domain (N-SH2) can also keep the enzyme inactive by intramolecular occlusion of the catalytic site. Enzyme activity can be recovered by an allosteric disruption of this self-inhibitory docking upon the binding of pY peptides to the N-SH2 domain. Prior to this, the N-SH2 domain must abandon the closed conformation because it impedes the access of pY peptides to the binding cleft. Although it cooperates with the self-inhibitory docking in the negative regulation of the phosphatase activity, the structural determinants of the stability of the closed conformation in the self-inhibited phosphatase are still elusive. To address this issue, a molecular dynamics simulation study is carried out. It is shown that the closed conformation is stabilized by the interaction of the N-SH2 domain with a conserved peptide portion in the region encoded by
MeSH term(s)	Catalytic Domain ; Molecular Dynamics Simulation ; Peptides/chemistry ; Phosphotyrosine/metabolism ; Protein Binding ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism ; src Homology Domains
Chemical Substances	Peptides ; Phosphotyrosine (21820-51-9) ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 (EC 3.1.3.48)
Language	English
Publishing date	2022-04-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23094794
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Article ; Online: Mutations Causing Mild or No Structural Damage in Interfaces of Multimerization of the Fibrinogen γ-Module More Likely Confer Negative Dominant Behaviors.

Bellacchio, Emanuele

International journal of molecular sciences

2020 Volume 21, Issue 23

Abstract: Different pathogenic variants in the same protein or even within the same domain of a protein may differ in their patterns of disease inheritance, with some of the variants behaving as negative dominant and others as autosomal recessive mutations. Here ... ...

Abstract	Different pathogenic variants in the same protein or even within the same domain of a protein may differ in their patterns of disease inheritance, with some of the variants behaving as negative dominant and others as autosomal recessive mutations. Here is presented a structural analysis and comparison of the molecular characteristics of the sites in fibrinogen γ-module, a fibrinogen component critical in multimerization processes, targeted by pathogenic variants (HGMD database) and by variants found in the healthy population (gnomAD database). The main result of this study is the identification of the molecular pathogenic mechanisms defining which pattern of disease inheritance is selected by mutations at the crossroad of autosomal recessive and negative dominant modalities. The observations in this analysis also warn about the possibility that several variants reported in the non-pathogenic gnomAD database might indeed be a hidden source of diseases with autosomal recessive inheritance or requiring a combination with other disease-causing mutations. Disease presentation might remain mostly unrevealed simply because the very low variant frequency rarely results in biallelic pathogenic mutations or the coupling with mutations in other genes contributing to the same disease. The results here presented provide hints for a deeper search of pathogenic mechanisms and modalities of disease inheritance for protein mutants participating in multimerization phenomena.
MeSH term(s)	Amino Acids/chemistry ; Databases, Genetic ; Fibrinogens, Abnormal/chemistry ; Fibrinogens, Abnormal/genetics ; Gene Frequency/genetics ; Genes, Dominant ; Humans ; Models, Molecular ; Mutation/genetics ; Mutation, Missense/genetics ; Protein Multimerization
Chemical Substances	Amino Acids ; Fibrinogens, Abnormal ; fibrinogen gamma'
Language	English
Publishing date	2020-11-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21239016
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Article ; Online: The Recruitment-Secretory Block ("R-SB") Phenomenon and Endoplasmic Reticulum Storage Diseases.

Callea, Francesco / Tomà, Paolo / Bellacchio, Emanuele

International journal of molecular sciences

2021 Volume 22, Issue 13

Abstract: In this article, we review the biological and clinical implication of the Recruitment-Secretory Block ("R-SB") phenomenon. The phenomenon refers to the reaction of the liver with regard to protein secretion in conditions of clinical stimulation. Our ... ...

Abstract	In this article, we review the biological and clinical implication of the Recruitment-Secretory Block ("R-SB") phenomenon. The phenomenon refers to the reaction of the liver with regard to protein secretion in conditions of clinical stimulation. Our basic knowledge of the process is due to the experimental work in animal models. Under basal conditions, the protein synthesis is mainly carried out by periportal (zone 1) hepatocytes that are considered the "professional" synthesizing protein cells. Under stimulation, midlobular and centrolobular (zones 2 and 3) hepatocytes, are progressively recruited according to lobular gradients and contribute to the increase of synthesis and secretion. The block of secretion, operated by exogenous agents, causes intracellular retention of all secretory proteins. The Pi MZ phenotype of Alpha-1-antitrypsin deficiency (AATD) has turned out to be the key for in vivo studies of the reaction of the liver, as synthesis and block of secretion are concomitant. Indeed, the M fraction of AAT is stimulated for synthesis and regularly exported while the Z fraction is mostly retained within the cell. For that reason, the phenomenon has been designated "Recruitment-Secretory Block" ("R-SB"). The "R-SB" phenomenon explains why: (a) the MZ individuals can correct the serum deficiency; (b) the resulting immonohistochemical and electron microscopic (EM) patterns are very peculiar and specific for the diagnosis of the Z mutation in tissue sections in the absence of genotyping; (c) the term carrier is no longer applicable for the heterozygous condition as all Pi MZ individuals undergo storage and the storage predisposes to liver damage. The storage represents the true elementary lesion and consequently reflects the phenotype-genotype correlation; (d) the site and function of the extrahepatic AAT and the relationship between intra and extracellular AAT; (e) last but not least, the concept of Endoplasmic Reticulum Storage Disease (ERSD) and of a new disease, hereditary hypofibrinogenemia with hepatic storage (HHHS). In the light of the emerging phenomenon, described in vitro, namely that M and Z AAT can form heteropolymers within hepatocytes as well as in circulation, we have reviewed the whole clinical and experimental material collected during forty years, in order to evaluate to what extent the polymerization phenomenon occurs in vivo. The paper summarizes similarities and differences between AAT and Fibrinogen as well as between the related diseases, AATD and HHHS. Indeed, fibrinogen gamma chain mutations undergo an aggregation process within the RER of hepatocytes similar to AATD. In addition, this work has clarified the intriguing phenomenon underlying a new syndrome, hereditary hypofibrinogenemia and hypo-APO-B-lipoproteinemia with hepatic storage of fibrinogen and APO-B lipoproteins. It is hoped that these studies could contribute to future research and select strategies aimed to simultaneously correct the hepatocytic storage, thus preventing the liver damage and the plasma deficiency of the two proteins.
MeSH term(s)	Animals ; Animals, Genetically Modified ; Biomarkers ; Disease Models, Animal ; Disease Susceptibility ; Endoplasmic Reticulum/metabolism ; Genetic Predisposition to Disease ; Humans ; Liver/metabolism ; Liver/pathology ; Liver/ultrastructure ; Metabolic Networks and Pathways ; Metabolism, Inborn Errors/genetics ; Metabolism, Inborn Errors/metabolism ; Protein Translocation Systems/metabolism ; Protein Transport ; alpha 1-Antitrypsin/genetics ; alpha 1-Antitrypsin/metabolism ; alpha 1-Antitrypsin Deficiency/genetics ; alpha 1-Antitrypsin Deficiency/metabolism
Chemical Substances	Biomarkers ; Protein Translocation Systems ; alpha 1-Antitrypsin
Language	English
Publishing date	2021-06-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22136807
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Article ; Online: Analysis of the

Cudini, Annamaria / Nardella, Caterina / Bellacchio, Emanuele / Palma, Alessia / Delfino, Domenico Vittorio / Betterle, Corrado / Cappa, Marco / Fierabracci, Alessandra

International journal of molecular sciences

2024 Volume 25, Issue 5

Abstract: Autoimmune polyglandular syndromes (APS) are classified into four main categories, APS1-APS4. APS1 is caused ... ...

Abstract	Autoimmune polyglandular syndromes (APS) are classified into four main categories, APS1-APS4. APS1 is caused by
MeSH term(s)	Humans ; Polyendocrinopathies, Autoimmune ; Syndrome ; Mutation ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic
Language	English
Publishing date	2024-02-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25052656
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Article ; Online: In silico analysis of the two tandem somatomedin B domains of ENPP1 reveals hints on the homodimerization of the protein.

Bellacchio, Emanuele

Journal of cellular physiology

2012 Volume 227, Issue 11, Page(s) 3566–3574

Abstract: The homodimerization of ENPP1 is mediated by the two somatomedin B (SMB) domains of the protein through a mechanism that is yet unknown at the atomistic level. The tandem arrangement of these domains without an intermediate spacer implies their possible ... ...

Abstract	The homodimerization of ENPP1 is mediated by the two somatomedin B (SMB) domains of the protein through a mechanism that is yet unknown at the atomistic level. The tandem arrangement of these domains without an intermediate spacer implies their possible packing into a functional assembly, which we explored by rigid docking. To exclude potential bias in the docking search we assessed the absence of flexible protein regions by evaluating the normalized B-factors calculated from the Cα atom displacements derived from molecular dynamics simulations. After filtering the docking results exploiting the criterion that residues located at the inter-domain interfaces are more conserved than non-interface residues, the resulting best model of the tandem SMB domains revealed the presence of two large conserved surface patches not engaged in the inter-domain contact. The largest patch is flat and contains all the invariant positively charged residues characterized by fully solvent-exposed side chains within the tandem SMB domains, suggesting as a possible role its interaction with the negative phospholipids on the cell surface. We envisage that an ENPP1 monomer bound to the cell membrane via the transmembrane segment can also interact with the cell surface through the largest conserved patch favoring a specific geometry of the tandem SMB module on the cell that optimally exposes the second conserved patch for the symmetric interaction with another membrane-bound ENPP1 monomer, finally promoting the homodimerization. Biological implications of this model and insights into the effects of the K173Q variant associated with insulin resistance and related abnormalities are presented.
MeSH term(s)	Amino Acid Sequence ; Animals ; Carbon/chemistry ; Genetic Variation ; Humans ; Insulin Resistance/genetics ; Insulin Resistance/physiology ; Mice ; Models, Molecular ; Molecular Dynamics Simulation ; Molecular Sequence Data ; Phosphoric Diester Hydrolases/chemistry ; Phosphoric Diester Hydrolases/genetics ; Phosphoric Diester Hydrolases/metabolism ; Protein Conformation ; Protein Interaction Domains and Motifs ; Protein Multimerization ; Pyrophosphatases/chemistry ; Pyrophosphatases/genetics ; Pyrophosphatases/metabolism ; Sequence Alignment ; Somatomedins/chemistry ; Somatomedins/genetics ; Somatomedins/metabolism
Chemical Substances	Somatomedins ; somatomedin B (63774-77-6) ; Carbon (7440-44-0) ; Phosphoric Diester Hydrolases (EC 3.1.4.-) ; ectonucleotide pyrophosphatase phosphodiesterase 1 (EC 3.1.4.1) ; Pyrophosphatases (EC 3.6.1.-)
Language	English
Publishing date	2012-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.24058
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Article: Novel loss of function mutation in

Zocchi, Riccardo / Bellacchio, Emanuele / Piccione, Michela / Scardigli, Raffaella / D'Oria, Valentina / Petrini, Stefania / Baranano, Kristin / Bertini, Enrico / Sferra, Antonella

Frontiers in cellular neuroscience

2023 Volume 17, Page(s) 1162363

Abstract: Microtubules are dynamic cytoskeletal structures involved in several cellular functions, such as intracellular trafficking, cell division and motility. More than other cell types, neurons rely on the proper functioning of microtubules to conduct their ... ...

Abstract	Microtubules are dynamic cytoskeletal structures involved in several cellular functions, such as intracellular trafficking, cell division and motility. More than other cell types, neurons rely on the proper functioning of microtubules to conduct their activities and achieve complex morphologies. Pathogenic variants in genes encoding for α and β-tubulins, the structural subunits of microtubules, give rise to a wide class of neurological disorders collectively known as "tubulinopathies" and mainly involving a wide and overlapping range of brain malformations resulting from defective neuronal proliferation, migration, differentiation and axon guidance. Although tubulin mutations have been classically linked to neurodevelopmental defects, growing evidence demonstrates that perturbations of tubulin functions and activities may also drive neurodegeneration. In this study, we causally link the previously unreported missense mutation p.I384N in TUBA1A, one of the neuron-specific α-tubulin isotype I, to a neurodegenerative disorder characterized by progressive spastic paraplegia and ataxia. We demonstrate that, in contrast to the p.R402H substitution, which is one of the most recurrent TUBA1A pathogenic variants associated to lissencephaly, the present mutation impairs TUBA1A stability, reducing the abundance of TUBA1A available in the cell and preventing its incorporation into microtubules. We also show that the isoleucine at position 384 is an amino acid residue, which is critical for α-tubulin stability, since the introduction of the p.I384N substitution in three different tubulin paralogs reduces their protein level and assembly into microtubules, increasing their propensity to aggregation. Moreover, we demonstrate that the inhibition of the proteasome degradative systems increases the protein levels of TUBA1A mutant, promoting the formation of tubulin aggregates that, as their size increases, coalesce into inclusions that precipitate within the insoluble cellular fraction. Overall, our data describe a novel pathogenic effect of p.I384N mutation that differs from the previously described substitutions in
Language	English
Publishing date	2023-06-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2023.1162363
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Article: Mechanism of neurotoxicity of prion and Alzheimer's disease-related proteins: molecular insights from bioinformatically identified ω-conotoxin-like pharmacophores.

Bellacchio, Emanuele

Critical reviews in eukaryotic gene expression

2009 Volume 23, Issue 4, Page(s) 355–373

Abstract: Prion diseases are fatal neurodegenerative disorders caused by altered forms of the prion protein (PrPC). It was reported that dysregulation of cellular Ca2+ homeostasis is recurrent in these diseases and that scrapie-infected cells exhibit Ca2+ ... ...

Abstract	Prion diseases are fatal neurodegenerative disorders caused by altered forms of the prion protein (PrPC). It was reported that dysregulation of cellular Ca2+ homeostasis is recurrent in these diseases and that scrapie-infected cells exhibit Ca2+ perturbation via specific impairment of N-type calcium channels. However, it is not known whether such dysfunction is secondary to the broad neuronal damage accompanying prion diseases or whether it underlies pathological interactions of prions with calcium channels. In this research, we examined this latter possibility by searching for channel binding signatures in PrPC through structural comparison with known N-type channel blockers. To this aim, a computational method devised by us to recognize similar distributions of basic residues in protein structures enabled us to find that the bioactive groups representing the pharmacophores of ω-conotoxins GVIA and MVIIA can be overlaid onto similar residues within the PrPC globular domain. This finding, together with the knowledge that Ca2+ homeostasis disruption is common to other neurodegenerative disorders, led us to search for and identify an ω-conotoxin-like pharmacophore also in the Alzheimer's Aβ(1-42) peptide. These results point to the potential ability of prions and Aβ(1-42) to bind calcium channels as the elusive neurotoxic mechanism common to seemingly unrelated fatal neuropathies.
MeSH term(s)	Amyloid beta-Peptides/chemistry ; Animals ; Computational Biology ; Humans ; Models, Molecular ; Peptide Fragments/chemistry ; Prions/chemistry ; Protein Structure, Tertiary ; omega-Conotoxins/chemistry
Chemical Substances	Amyloid beta-Peptides ; Peptide Fragments ; Prions ; amyloid beta-protein (1-42) ; omega-Conotoxins
Language	English
Publishing date	2009-01-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1071345-1
ISSN	1045-4403
ISSN	1045-4403
DOI	10.1615/critreveukaryotgeneexpr.2013007950
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Article ; Online: Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation.

Callea, Francesco / Francalanci, Paola / Grimaldi, Chiara / Camassei, Francesca Diomedi / Devito, Rita / Facchetti, Fabio / Alaggio, Rita / Bellacchio, Emanuele

International journal of molecular sciences

2022 Volume 23, Issue 17

Abstract: Seventeen out of 764 liver biopsies from transplanted (Tx) livers in children showed glycogen-ground glass (GGG) hepatocytic inclusions. The inclusions were not present in pre-Tx or in the explanted or donor's liver. Under the electron microscope (EM), ... ...

Abstract	Seventeen out of 764 liver biopsies from transplanted (Tx) livers in children showed glycogen-ground glass (GGG) hepatocytic inclusions. The inclusions were not present in pre-Tx or in the explanted or donor's liver. Under the electron microscope (EM), the stored material within the cytosol appeared as non-membrane-bound aggregates of electron-lucent globoid or fibrillar granules, previously described as abnormally structured glycogen and identified as Polyglucosan bodies (PB). The appearance of GGG in our children was analogous to that of PB-GGG occurring in a number of congenital diseases due to gene mutations such as Lafora's d., Andersen's d., Adult Polyglucosan Body Disease and glycogenin deficiency. The same type of GGG was previously reported in the liver of patients undergoing transplants, immunosuppressive or antiblastic treatment. To explore the potential mechanism of GGG formation, we examined whether the drugs after whose treatment this phenomenon was observed could have a role. By carrying out molecular docking, we found that such drugs somehow present a high binding affinity for the active region of glycogenin, implicating that they can inactivate the protein, thus preventing its interaction with glycogen synthase (GS), as well as the maturation of the nascent glycogen towards gamma, beta or alfa glycogen granules. We could also demonstrate that PG inclusions consist of a complex of PAS positive material (glycogen) and glycogen-associated proteins, i.e., glicogenin-1 and -2 and ubiquitin. These features appear to be analogous to congenital GGG, suggesting that, in both cases, they result from the simultaneous dysregulation of glycogen synthesis and degradation. Drug-induced GGG appear to be toxic to the cell, despite their reversibility.
MeSH term(s)	Child ; Glucans/metabolism ; Glycogen/metabolism ; Humans ; Liver Transplantation ; Molecular Docking Simulation
Chemical Substances	Glucans ; Glycogen (9005-79-2) ; polyglucosan (9012-72-0)
Language	English
Publishing date	2022-09-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23179996
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Article ; Online: Functional analysis of missense DARS2 variants in siblings with leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation.

Wongkittichote, Parith / Magistrati, Martina / Shimony, Joshua S / Smyser, Christopher D / Fatemi, Seyed Ali / Fine, Amena S / Bellacchio, Emanuele / Dallabona, Cristina / Shinawi, Marwan

Molecular genetics and metabolism

2022 Volume 136, Issue 4, Page(s) 260–267

Abstract: Biallelic pathogenic variants in the nuclear gene DARS2 (MIM# 610956), encoding the mitochondrial enzyme aspartyl-tRNA synthetase (MT-ASPRS) cause leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation (LBSL) (MIM# 611105), ...

Abstract	Biallelic pathogenic variants in the nuclear gene DARS2 (MIM# 610956), encoding the mitochondrial enzyme aspartyl-tRNA synthetase (MT-ASPRS) cause leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Lactate Elevation (LBSL) (MIM# 611105), a neurometabolic disorder characterized by progressive ataxia, spasticity, developmental arrest or regression and characteristic brain MRI findings. Most patients exhibit a slowly progressive disease course with motor deterirartion that begins in childhood or adolescence, but can also occasionaly occur in adulthood. More severe LBSL presentations with atypical brain MRI findings have been recently described. Baker's yeast orthologue of DARS2, MSD1, is required for growth on oxidative carbon sources. A yeast with MSD1 knockout (msd1Δ) demonstrated a complete lack of oxidative growth which could be rescued by wild-type MSD1 but not MSD1 with pathogenic variants. Here we reported two siblings who exhibited developmental regression and ataxia with different age of onset and phenotypic severity. Exome sequencing revealed 2 compound heterozygous missense variants in DARS2: c.473A>T (p.Glu158Val) and c.829G>A (p.Glu277Lys); this variant combination has not been previously reported. The msd1Δ yeast transformed with plasmids expressing p.Glu259Lys, equivalent to human p.Glu277Lys, showed complete loss of oxidative growth and oxygen consumption, while the strain carrying p.Gln137Val, equivalent to human p.Glu158Val, showed a significant reduction of oxidative growth, but a residual ability to grow was retained. Structural analysis indicated that p.Glu158Val may interfere with protein binding of tRNA
MeSH term(s)	Adolescent ; Adult ; Aspartate-tRNA Ligase/genetics ; Ataxia/pathology ; Brain Stem/metabolism ; Brain Stem/pathology ; Disease Progression ; Humans ; Lactic Acid ; Leukoencephalopathies/diagnostic imaging ; Leukoencephalopathies/genetics ; Mutation ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Siblings ; Spinal Cord/diagnostic imaging ; Spinal Cord/metabolism ; Spinal Cord/pathology
Chemical Substances	Lactic Acid (33X04XA5AT) ; Aspartate-tRNA Ligase (EC 6.1.1.12) ; DARS2 protein, human (EC 6.1.1.12)
Language	English
Publishing date	2022-07-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1418518-0
ISSN	1096-7206 ; 1096-7192
ISSN (online)	1096-7206
ISSN	1096-7192
DOI	10.1016/j.ymgme.2022.07.002
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