Lysosomal Storage Disorders Research

ASM Variants in the Spotlight: A Structure-Based Atlas for Unraveling Pathogenic Mechanisms in Lysosomal Acid Sphingomyelinase

The paper creates a structural atlas of ASM variants to understand their pathogenic mechanisms and therapeutic implications.

Heterologous HSPC transplantation rescues neuroinflammation and ameliorates peripheral manifestations in the mouse model of lysosomal transmembrane enzyme deficiency, MPS IIIC.

This study shows that heterologous HSPC transplantation reduces neuroinflammation and improves peripheral symptoms in a mouse model of MPS IIIC, but does not correct lysosomal storage in neurons.

Direct and indirect regulation of β- glucocerebrosidase by the transcription factors USF2 and ONECUT2

The paper identifies transcription factors that regulate β-glucocerebrosidase activity, showing that USF2 and ONECUT2 have opposing effects on GCase levels and function.

Smpd1 regulates chitin-clearance for tracheal gas-filling in the Drosophila embryo in a ceramide-specific manner

This study identifies Smpd1's role in tracheal gas-filling in Drosophila embryos by regulating ceramide-specific chitin-clearance, showing that lipid metabolism defects contribute to respiratory dysfunction.

GM1 Gangliosidosis Type II: Results of a 10-Year Prospective Study

This study presents a 10-year prospective analysis of type II GM1 gangliosidosis, detailing disease progression and phenotypic features in 41 patients.

Endothelial and neuronal engagement by AAV-BR1 alleviates neurological symptoms and cholesterol deposition in a mouse model of Niemann-Pick type C2

AAV-BR1-NPC2 gene therapy reduces cholesterol deposition and neurological symptoms in NP-C2 mice by delivering NPC2 to brain endothelial cells and neurons.

Early striatal hyperexcitability in an in vitro human striatal microcircuit model carrying the Parkinson's GBA-N370S mutation

This study shows that the GBA-N370S mutation causes early hyperexcitability in striatal neurons by reducing sodium and potassium currents, which can be mitigated by aging or PKA antagonism.

GABAAR-PPT1 palmitoylation homeostasis controls synaptic transmission and circuitry oscillation in CLN1 disease

This study identifies PPT1's role in regulating GABAAR palmitoylation, showing its impact on synaptic transmission and circuitry oscillation in CLN1 disease.

Cellular Modeling of CLN6 with IPSC-derived Neurons and Glia

The paper develops CLN6 patient-derived iPSC models to study neurodegeneration, finding significant lysosomal and synaptic pathway changes in differentiated neurons.

CLN3 deficiency leads to neurological and metabolic perturbations during early development

This study shows that CLN3 deficiency in zebrafish leads to metabolic changes, including GPD accumulation and BMP reduction, and confirms these findings in human stem cell models.

Preclinical studies with ground germinated barley (GGB) for oral enzyme replacement therapy (Oral-ERT) in Pompe disease knockout mice

This paper investigates the use of ground germinated barley (GGB) as an oral enzyme replacement therapy (Oral-ERT) for Pompe disease in knockout mice, showing it can reverse enzyme defects and improve clinical phenotypes.

Gba1 deletion causes immune hyperactivation and microbial dysbiosis through autophagic defects

This study shows that Gba1 deletion in flies causes immune hyperactivation and microbial dysbiosis, which can be mitigated by microbiome modulation or autophagy stimulation.

Severe Central Nervous System Demyelination in Sanfilippo Disease

This study investigates white matter injury in Sanfilippo disease using mouse models and human samples, revealing demyelination and specific MRI markers for disease progression.

CLN3 transcript complexity revealed by long-read RNA sequencing analysis

The paper uses long-read RNA sequencing to analyze CLN3 transcript complexity in healthy samples, identifying over 100 novel transcripts and 48 ORFs, with the canonical isoform being the most abundant.

Sortilin inhibition treats multiple neurodegenerative lysosomal storage disorders.

This study shows that sortilin inhibition with AF38469 improves lysosomal and glial pathology in multiple Batten disease models.

Longitudinal Deep Multi-Omics Profiling in a CLN3Δex7/8 Minipig Model Reveals Novel Biomarker Signatures for Batten Disease

Inflammation and autophagy dysfunction in metachromatic leukodystrophy: a central role for mTOR?

This study identifies inflammation and autophagy dysfunction, linked to mTOR pathway activation, as key mechanisms in metachromatic leukodystrophy using postmortem tissue analysis.

Linking Gba1 E326K mutation to microglia activation and mild age-dependent dopaminergic Neurodegeneration

This study investigates the effects of Gba1 E326K mutation in mice, showing increased microglia activation, neuroinflammation, and dopaminergic neurodegeneration.

Characterization of Novel Human β-glucocerebrosidase Antibodies for Parkinson Disease Research

This study characterizes two novel human GCase antibodies for use in various assays to advance Parkinson disease research.

Neural-specific alterations in glycosphingolipid biosynthesis and cell signaling associated with two human ganglioside GM3 Synthase Deficiency variants

This study investigates how two ST3GAL5 variants cause GM3SD by analyzing GSL biosynthesis and signaling changes in patient-derived iPSCs and NCCs.

Small fibre neuropathy in Fabry disease: a human-derived neuronal in vitro disease model

This study creates a neuronal in vitro model of Fabry disease to investigate small fibre neuropathy mechanisms, finding Gb3 accumulation, altered ion channel function, and mitochondrial trafficking issues.

Challenging the Conventional Treatment Initiation Paradigm: Early Detection of Irreversible Cellular Damage in Cardiac Biopsies of Fabry Disease Before the Formation of Gb3 Inclusion Bodies

This study shows that cardiac biopsies from Fabry disease patients exhibit significant cellular stress and irreversible damage before Gb3 inclusion bodies form, suggesting earlier treatment initiation is needed.

Zebrafish models of Mucopolysaccharidosis IIIA, IIIB, and IIIC show hyperactivity, neuroinflammation and changes in oligodendrocyte cell state

This study creates zebrafish models of MPS IIIA, IIIB, and IIIC, revealing hyperactivity, neuroinflammation, and oligodendrocyte changes similar to human disease.

HDAC-6 inhibition ameliorates the early neuropathology in a mouse model of Krabbe disease

This study shows that HDAC6 inhibition with ACY-738 improves early neuropathology and neuronal defects in a mouse model of Krabbe disease.

Altered GM1 catabolism affects NMDAR-mediated Ca2+ signaling at ER-PM junctions and increases synaptic spineformation

This study shows that altered GM1 catabolism disrupts ER-PM junctions, increases Ca2+ signaling, and promotes synaptic spine formation in a neurodegenerative disease model.

NGLY1 Deficiency: A Prospective Natural History Study (NHS)

This study tracks the clinical progression of NGLY1 Deficiency in 29 patients over 32 months, identifying key symptoms and biomarkers for future trial endpoints.

A novel porcine model of CLN3 Batten disease recapitulates clinical phenotypes

This paper presents a novel porcine model of CLN3 Batten disease that recapitulates clinical phenotypes observed in humans.

Osteonecrosis in Gaucher Disease in the era of multiple therapies: biomarker set for risk stratification from a tertiary referral center

This study identifies biomarkers predicting avascular osteonecrosis risk in Gaucher disease patients on enzyme replacement or substrate reduction therapy.

Bowel dysmotility and enteric neuron degeneration in lysosomal storage disease mice is prevented by gene therapy

This paper shows gene therapy prevents bowel motility issues and enteric neuron loss in mouse models of lysosomal storage diseases.

Glucocerebrosidase activity and lipid levels are related to protein pathologies in Parkinson's disease

The paper examines the relationship between glucocerebrosidase activity, lipid levels, and protein pathologies in Parkinson's disease and dementia with Lewy bodies.