gba

BACKGROUND: The GPNMB single-nucleotide polymorphism rs199347 and GBA1 variants both associate with Lewy body disorder (LBD) risk. GPNMB encodes glycoprotein nonmetastatic melanoma protein B (GPNMB), a biomarker for GBA1-associated Gaucher's disease. OBJECTIVE: The aim of this study was to determine whether GPNMB levels (1) differ in LBD with and without GBA1 variants and (2) associate with rs199347 genotype. METHODS: We quantified GPNMB levels in plasma and cerebrospinal fluid (CSF) from 124 individuals with LBD with one GBA1 variant (121 plasma, 14 CSF), 631 individuals with LBD without GBA1 variants (626 plasma, 41 CSF), 9 neurologically normal individuals with one GBA1 variant (plasma), and 2 individuals with two GBA1 variants (plasma)...

Understanding medium spiny neuron (MSN) physiology is essential to understand motor impairments in Parkinson's disease (PD) given the architecture of the basal ganglia. Here, we developed a custom three-chambered microfluidic platform and established a cortico-striato-nigral microcircuit partially recapitulating the striatal presynaptic landscape in vitro using induced pluripotent stem cell (iPSC)-derived neurons. We found that, cortical glutamatergic projections facilitated MSN synaptic activity, and dopaminergic transmission enhanced maturation of MSNs in vitro...

Parkinson's disease (PD) is a common neurodegenerative disease with progressive loss of dopaminergic neurons in substantia nigra and the presence of α-synuclein-immunoreactive inclusions. Gaucher's disease is caused by homozygous mutations in β-glucocerebrosidase gene (GBA). GBA mutation carriers have an increased risk of PD. Coptis chinensis (C. chinensis) rhizome extract is a major herb widely used to treat human diseases. This study examined the association of GBA L444P mutation with Taiwanese PD in 1016 cases and 539 controls...

Transcription factor EB (TFEB) is a master regulator of genes involved in the maintenance of autophagic and lysosomal homeostasis, processes which have been implicated in the pathogenesis of GBA-related and sporadic Parkinson's disease (PD), and dementia with Lewy bodies (DLB). TFEB activation results in its translocation from the cytosol to the nucleus. Here, we investigated TFEB subcellular localization and its relation to intracellular alpha-synuclein (aSyn) accumulation in post-mortem human brain of individuals with either incidental Lewy body disease (iLBD), GBA-related PD/DLB (GBA-PD/DLB) or sporadic PD/DLB (sPD/DLB), compared to control subjects...

This retrospective study aimed to explore the therapeutic potential of Bifidobacterium bifidum supplementation on elderly ischemic stroke patients. We retrospectively analyzed electronic medical records from 153 elderly ischemic stroke patients. Patients were stratified into 2 groups: those receiving B bifidum supplementation (Intervention group, n = 73) and those receiving standard treatment without any additional supplementation (Control group, n = 80). Outcomes were assessed using the National Institutes of Health Stroke Scale (NIHSS), Montreal Cognitive Assessment (MoCA), Self-Rating Depression Scale (SDS), and Self-Rating Anxiety Scale (SAS)...

The gut-brain axis (GBA) is an important information pathway connecting the brain, the central nervous system (CNS), and the gastrointestinal (GI) tract. On the one hand, gut microbiota can influence the function brain through GBA; on the other hand, the brain can also change the structural composition of gut microbiota via GBA. It contains a myriad of biosignals, such as monoamines, inflammatory cytokines, and macro-biomolecules, as the information carriers. Highly selective, sensitive, and reliable sensing techniques are essential to resolve the specific function of individual biosignals...

OBJECTIVES: Data scarcity and domain shifts lead to biased training sets that do not accurately represent deployment conditions. A related practical problem is cross-modal image segmentation, where the objective is to segment unlabelled images using previously labelled datasets from other imaging modalities. METHODS: We propose a cross-modal segmentation method based on conventional image synthesis boosted by a new data augmentation technique called Generative Blending Augmentation (GBA)...

As a major carbon emitter, the power sector plays a crucial role in realizing the goal of carbon peaking and carbon neutrality. This study constructed a low-carbon power system based on the LEAP model (LEAP-GBA) with 2020 as a statistic base aiming of exploring the low-carbon transformation pathway of the power sector in the Guangdong-Hong Kong, and Macao Greater Bay Area (GBA). Five scenarios are set up to simulate the demand, power generation structure, carbon emissions, and power generation costs in the power sector under different scenarios...

Heterozygous carriers of the glucocerebrosidase 1 (GBA) L444P Gaucher mutation have an increased risk of developing Parkinson's disease (PD). The GBA mutations result in elevated alpha synuclein (aSyn) levels. Heterozygous mice carrying one allele with the L444P mutation knocked-into the mouse gene show increased aSyn levels and are more sensitive to motor deficits following exposure to the neurotoxin (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) MPTP than wild-type mice. Paraquat (PQ), a herbicide, increases PD risk in most studies...

The gut-brain axis (GBA) plays a significant role in various neurodegenerative disorders, such as Alzheimer's disease (AD), and the gut microbiome (GM) can bidirectionally communicate with the brain through the GBA. Thus, recent evidence indicates that the GM may affect the pathological features and the progression of AD in humans. The aim of our study was to elucidate the impact of probiotics on the pathological features of AD in a 5xFAD model. Probiotics ( Bifidobacterium lactis , Levilactobacillus brevis , and Limosilactobacillus fermentum ) were orally administered in 5xFAD mice to modify the GM composition...

A remarkable progress has been made toward the air quality improvements over the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) of China from 2017 to 2020. In this study, for the first time, the emission reductions of regional control measures together with the COVID-19 pandemic were considered simultaneously into the development of the GBA's emission inventories for the years of 2017 and 2020. Based on these collective emission inventories, the impacts of control measures, meteorological variations together with temporary COVID-19 lockdowns on the five major air quality index pollutants (SO2 , NO2 , PM2...

Plant height (PH) is an important factor affecting bast fiber yield in jute. Here, we report the mechanism of dwarfism in the 'Guangbaai' (gba) of jute. The mutant gba had shorter internode length and cell length compared to the standard cultivar 'TaiZi 4' (TZ4). Exogenous GA3 treatment indicated that gba is a GA-insensitive dwarf mutant. Quantitative trait locus (QTL) analysis of three PH-related traits via a high-density genetic linkage map according to re-seq showed that a total of 25 QTLs were identified, including 13 QTLs for PH, with phenotypic variation explained ranging from 2...

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Genome-wide association studies have successfully identified many genetic risk loci for dementia, but exact biological mechanisms through which genetic risk factors contribute to dementia remains unclear. Integrating CSF proteomic data with dementia risk loci could reveal intermediate molecular pathways connecting genetic variance to the development of dementia. We tested to what extent effects of known dementia risk loci can be observed in CSF levels of 665 proteins (proximity extension-based (PEA) immunoassays) in a deeply-phenotyped mixed-memory clinic cohort (n=502, mean age (sd) = 64...

There is an urgent requirement to acquire a comprehensive comprehension of novel therapeutic targets for prostate cancer to facilitate the development of medications with innovative mechanisms. In this study, we identified gambogic acid (GBA) as a specific pyroptosis inducer in prostatic cancer cells. By using a thermal proteome profiling (TPP) strategy, we revealed that GBA induces pyroptosis by directly targeting the canopy FGF signaling regulator (CNPY3), which was previously considered "undruggable". Moreover, through the utilization of the APEX2-based proximity labeling method, we found that GBA recruited delactatease SIRT1, resulting in the elimination of lysine lactylation (Kla) on CNPY3...

 The movement toward prevention trials in people at-risk for Parkinson's disease (PD) is rapidly becoming a reality. The authors of this article include a genetically at-risk advocate with the LRRK2 G2019 S variant and two patients with rapid eye movement sleep behavior disorder (RBD), one of whom has now been diagnosed with PD. These authors participated as speakers, panelists, and moderators in the "Planning for Prevention of Parkinson's: A Trial Design Forum" hosted by Massachusetts General Hospital in 2021 and 2022...

Gaucher disease (GD) is a lysosomal storage disorder caused by glucocerebrosidase (GBA) deficiency. There are three subcategories of GD: Type 1 is characterized by the absence of primary central nervous system involvement; type 2 is an acute neuropathic disorder; and type 3 is chronic neuropathic. The correlation between genotype and phenotype is sometimes difficult to establish. The F213I (c.754T>A p.Phe252Ile) mutation was reported to be a unique mutation in Asia. To our knowledge, this is the first time the c...

Amyotrophic Lateral Sclerosis (ALS) is a highly fatal neurodegenerative disorder characterized by the progressive wasting and paralysis of voluntary muscle. Despite extensive research, the etiology of ALS remains elusive, and effective treatment options are limited. However, recent evidence implicates gut dysbiosis and gut-brain axis (GBA) dysfunction in ALS pathogenesis. Alterations to the composition and diversity of microbial communities within the gut flora have been consistently observed in ALS patients...

Rare and common GBA variants are risk factors for both Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, the degree to which GBA variants are associated with neuropathological features in Lewy body disease (LBD) is unknown. Herein, we assessed 943 LBD cases and examined associations of 15 different neuropathological outcomes with common and rare GBA variants. Neuropathological outcomes included LBD subtype, presence of a high likelihood of clinical DLB (per consensus guidelines), LB counts in five cortical regions, tyrosine hydroxylase immunoreactivity in the dorsolateral and ventromedial putamen, ventrolateral substantia nigra neuronal loss, Braak neurofibrillary tangle (NFT) stage, Thal amyloid phase, phospho-ubiquitin (pS65-Ub) level, TDP-43 pathology, and vascular disease...

Gut microbiome alterations are associated with various cancers including brain tumours such as glioma and glioblastoma. The gut communicates with the brain via a bidirectional pathway known as the gut-brain axis (GBA) which is essential for maintaining homeostasis. The gut microbiota produces many metabolites including short chain fatty acids (SCFAs) and essential amino acids such as glutamate, glutamine, arginine and tryptophan. Through the modulation of these metabolites the gut microbiome is able to regulate several functions of brain cells, immune cells and tumour cells including DNA methylation, mitochondrial function, the aryl hydrocarbon receptor (AhR), T-cell proliferation, autophagy and even apoptosis...