Lysosomal Storage Disorders Research

The paper develops a human stem cell toolkit for studying lysosomal storage disorders by generating proteomic data from induced cortical and dopaminergic-like neurons.

This study investigates the effects of bromodomain protein inhibition in a mouse model of Niemann-Pick type C disease, finding sex-dependent therapeutic benefits in male mice.

This study measures CSF glucosylsphingosine (GlcSph) levels in Parkinson’s disease patients and finds elevated GlcSph in GBA1 carriers and sporadic PD, indicating central GCase pathway impairment.

This study shows that targeting lysosomal pH with rapamycin or acidic nanoparticles restores mitochondrial function in GBA1-mutant Parkinson's disease neurons.

This study uses functional ultrasound imaging to show pathway-specific functional and pathological changes in the visual system of young Cln3-/- mice before severe retinal degeneration.

This study identifies mitochondrial dysfunction and metabolic impairments in DHDDS-related juvenile parkinsonism and shows that NMN treatment improves symptoms in patient-derived organoids and clinical cases.

This study links age- and sex-dependent auditory neurophysiological deficits in Cln3-/- mice to region-specific lysosomal storage pathology in the auditory thalamocortical circuit.

This study establishes isogenic NPC1 and NPC2 models to reveal that HKDC1 regulates mitochondrial-lysosome contact in NPC1-deficient cells.

This paper creates a humanised GBA-L444P mouse model to study GBA1 mutations in Parkinson's, finding gain-of-function effects on dopamine release and loss-of-function effects on alpha-synuclein pathology.

This study finds the GBA1 p.E427K variant increases risk for synucleinopathies through a meta-analysis of case-control studies.

This study shows that CLN3 is essential for synaptic function in Batten disease and that early gene therapy can reverse synaptic deficits.

This study shows GD3S deficiency disrupts NKA and PMCA function in mouse brain by altering ganglioside and lipid raft composition, suggesting therapeutic potential through exogenous ganglioside administration.

The paper uses computational drug repurposing to identify N-acetylglucosamine as a potential therapy for CLN3 Batten disease, showing it reduces lipofuscin burden in cell models.

This study identifies shared and distinct lipid profile changes in amygdala from sporadic and GBA-associated Parkinson's Disease, linking lipid metabolism to alpha-synuclein and glucocerebrosidase activity.

This study identifies and validates serum protein biomarkers for Niemann-Pick disease, type C1, showing correlations with disease severity and response to therapy.

The paper identifies six potential biomarkers for CLN3 disease using proteomics data and machine learning, with some showing differential expression linked to disease progression.

This study investigates how the R39C mutation in sialin affects its lysosomal transport function by analyzing structural and dynamic changes in the protein.

The paper develops and validates a quantitative LC-MS/MS method for measuring heparan sulfate in CSF as a biomarker for MPS IIIA, showing high accuracy and reproducibility.

This study identifies BMP and LPG as biomarkers for CLN5 Batten disease using lipidomics, showing their depletion and elevation in disease models and patient samples.

This study evaluates the efficacy of systemic AAV9-hNPC1 gene therapy in NPC1 mouse models, finding that higher doses and earlier treatment improve survival and slow disease progression.

The paper identifies cell type-specific lysosomal dysfunction in GRN deficiency using LysoIP and mass spectrometry, revealing progranulin's role in lysosomal protein sorting.

The paper tests a synthetic peptide ACTH(4-7)PGP in MPS III mouse models, showing it improves synaptic function, reduces neuroinflammation, and extends lifespan.

This phase 1/2 trial evaluates AAV9 gene therapy for GM1 gangliosidosis Type II, showing safety and some biochemical and neuroimaging improvements.

The paper creates a cell-type-specific lysosome protein atlas in the brain, identifies SLC45A1 as a neuron-specific lysosomal protein, and shows its role in lysosomal function and neurodegeneration.

The paper develops a C. elegans model of SRD5A3-CDG and identifies atorvastatin as a potential repurposed therapy through a high-throughput screen.

This study shows that LLOMe forms amyloid structures inside lysosomes that mechanically rupture the lysosomal membrane, revealing a structural mechanism for lysosomal damage.

This study models GBA1 deficiency in neurons and astrocytes using iPSCs, revealing cell-type specific endolysosomal trafficking defects and -synucleinopathy in neurons, while astrocytes show neurotoxic reactivity.

This study identifies multiple cathepsins and progranulin that regulate prosaposin cleavage into saposins, which are critical for sphingolipid metabolism.

This paper shows that CLN3 disease causes enteric nervous system degeneration in humans and mice, which can be prevented by neonatal gene therapy in mice.