Results 21 to 30 of about 2,680 (134)

Unraveling A4GALT Mechanism and Its Modulation With Adamantyl‐Galactosylceramide Analogues: Advancing Fabry Disease Therapeutic Strategies

Angewandte Chemie, EarlyView.
A 310‐helix‐mediated conformational switch promotes a front‐face SNi‐like catalysis by human A4GALT. Mechanism‐guided design identifies AdaGalCer as a selective modulator of globotriaosylceramide (Gb3) biosynthesis, opening a clear route toward new Fabry disease therapeutics.
Nicky de Koster, Òscar Vidal‐Gironès, Rowan de Graaf, Ken Kok, Lindsey T. Lelieveld, Jackelien Hoogervorst, Maria J. Ferraz, José Pablo Rivas‐Fernández, Rob F. Lammers, Herman S. Overkleeft, Johannes M. F. G. Aerts, Rolf G. Boot, Carme Rovira, Marta Artola   +13 more
wiley   +2 more sources

Autophagic dysfunction and gut microbiota dysbiosis cause chronic immune activation in a Drosophila model of Gaucher disease.

PLoS Genetics, 2023
Mutations in the GBA1 gene cause the lysosomal storage disorder Gaucher disease (GD) and are the greatest known genetic risk factors for Parkinson's disease (PD).
Magda L Atilano, Alexander Hull, Catalina-Andreea Romila, Mirjam L Adams, Jacob Wildfire, Enric Ureña, Miranda Dyson, Jorge Ivan-Castillo-Quan, Linda Partridge, Kerri J Kinghorn   +9 more
doaj   +1 more source

A severe neurodegenerative disease with Lewy bodies and a mutation in the glucocerebrosidase gene

npj Parkinson's Disease, 2023
Several heterozygous variants of the glucocerebrosidase gene (GBA1) have been reported to increase the risk of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB).
Jussi O. T. Sipilä, Laura Kytövuori, Tuomas Rauramaa, Hugo Rauhamaa, Valtteri Kaasinen, Kari Majamaa   +5 more
doaj   +1 more source

Efficient GBA1 editing via HDR with ssODNs by outcompeting pseudogene-mediated gene conversion upon CRISPR/Cas9 cleavage

Frontiers in Genome Editing
IntroductionCRISPR/Cas9-edited induced pluripotent stem cells (iPSCs) are valuable research models for mechanistic studies. However, gene conversion between a gene-pseudogene pair that share high sequence identity and form direct repeats in proximity on ...
Joseph S. Lagas, Monica F. Sentmanat, Xiaoxia Cui   +2 more
doaj   +1 more source

Dermal Phospho-Alpha-Synuclein Deposition in Patients With Parkinson's Disease and Mutation of the Glucocerebrosidase Gene

Frontiers in Neurology, 2018
Heterozygous mutations in the glucocerebrosidase gene (GBA1) represent the most common genetic risk factor for Parkinson's disease (PD) and are histopathologically associated with a widespread load of alpha-synuclein in the brain.
Kathrin Doppler, Kathrin Brockmann, Annahita Sedghi, Isabel Wurster, Jens Volkmann, Wolfgang H. Oertel, Claudia Sommer   +6 more
doaj   +1 more source

The most common structural variant expected at the GBA1 locus may be detected by a simple amplification method: Implications for screening Parkinson’s disease variants

Clinical Parkinsonism & Related Disorders
Introduction: Recombinant alleles are responsible for a large part of Gaucher disease (GD) causing alterations. This is because GBA1, the gene involved in GD, has a 96 % homologous pseudogene, GBAP1, at a 1.6kb distance.
Roberto Rozenberg, Fabiano Tofoli de Araujo, Hsin Fen Chien, Egberto Reis Barbosa, Lygia V. Pereira   +4 more
doaj   +1 more source

GBA genotype-Parkinson’s phenotype correlation in a cohort of 252 Italian patients from the Tuscany region

Clinical Parkinsonism & Related Disorders
Introduction: heterozygous mutations in the glucocerebrosidase gene (GBA1), encoding the lysosomal enzyme β-glucocerebrosidase (GCase) are the most common genetic risk factor for Parkinson’s disease (PD).
Rodolfo Tonin, Silvia Ramat, Marina Rinaldi, Silvia Falliano, Federica Feo, Francesca Cardona, Camilla Matassini, Guido Mannaioni, Giulia Grigioni, Luca Caremani, Alessandra Govoni, Maria Luisa Della Bona, Giancarlo la Marca, Renzo Guerrini, Amelia Morrone   +14 more
doaj   +1 more source

Lysine acetyltransferase 8-mediated histone acetylation, regulated by GBA1, is associated with lysosomal function related to α-Synuclein pathology

Cell Death and Disease
Lysosomal defects are closely linked to Parkinson’s disease (PD). Mutations in the GBA1 gene, encoding the lysosomal enzyme glucocerebrosidase (GCase), are major genetic risk factors for PD.
Yifan Cao, Zhixiong Zhang, Xinbei Gu, Haifeng Lu, Jin Wu, Chuang Zhang, Xinyue Huang, Haitao Qin, Feng Liu, Zhenhua Liu, Beisha Tang, Xiaojun Lu, Haigang Ren, Hongyang Sun, Rui Wang, Guanghui Wang   +15 more
doaj   +1 more source

Generation and Treatment of a Novel Severe Model of Visceral Gaucher Disease by Genetic Therapy

Pharmaceutics
Background/Objectives: Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the GBA1 gene. Type 1 Gaucher disease is characterised by substrate accumulation in the visceral organs, which occurs in combination ...
Amy F. Geard, Giulia Massaro, Michael P. Hughes, Patrick Arbuthnot, Simon N. Waddington, Ahad A. Rahim   +5 more
doaj   +1 more source

Impact of Gba2 on neuronopathic Gaucher’s disease and α-synuclein accumulation in medaka (Oryzias latipes)

Molecular Brain, 2021
Homozygous mutations in the lysosomal glucocerebrosidase gene, GBA1, cause Gaucher’s disease (GD), while heterozygous mutations in GBA1 are a strong risk factor for Parkinson’s disease (PD), whose pathological hallmark is intraneuronal α-synuclein (asyn)
Etsuro Nakanishi, Norihito Uemura, Hisako Akiyama, Masato Kinoshita, Sawamura Masanori, Yosuke Taruno, Hodaka Yamakado, Shu-ichi Matsuzawa, Shunichi Takeda, Yoshio Hirabayashi, Ryosuke Takahashi   +10 more
doaj   +1 more source