Lysosomal Storage Disorders Research

A human lysosomal storage disorder toolkit for decoding proteome landscapes in cortical and dopaminergic-like induced neurons

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

Effects of bromodomain protein inhibition in a mouse model of Niemann-Pick type C disease

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.

CSF glucosylsphingosine is a central readout of GCase impairment across genetic and sporadic Parkinson’s disease

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.

Targeting Lysosomal pH Restores Mitochondrial Quality Control in GBA1-Mutant Parkinsons Disease

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

Functional ultrasound imaging reveals pathway-specific visual system reorganization in young Cln3-/- mice

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.

DHDDS-related juvenile parkinsonism is caused by impaired lipid metabolism, glycosylation, and mitochondrial dysfunction, which can be rescued by NAD⁺ treatment.

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.

Distinct Auditory Thalamocortical Pathologies Underlie Emerging Neurophysiological Dysfunction in a Cln3 Mouse Model of Batten Disease

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

HKDC1 contributes to aberrant lysosome-mitochondria contact in Niemann-Pick disease type C

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

A human GBA-L444P transgene drives early and persistent dopamine neurotransmission deficits and alpha-synuclein pathology in a mouse model of early Parkinson's disease

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.

The GBA1 p.E427K (p.E388K) Variant is a Risk Factor for Synucleinopathies: A Meta-Analysis

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

Reversible synaptic deficits in early-stage Batten disease

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

GD3 synthase deficiency disrupts Na+/K+-ATPase and plasma membrane Ca2+-ATPase function in mouse brain

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.

Computational drug repurposing identifies N-acetylglucosamine as a potential therapeutic compound for CLN3 Batten disease

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.

Shared and Distinct Lipid Profiles in amygdala from Sporadic and GBA-associated Parkinson's Diseases

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.

Identification of serum protein biomarkers in individuals with Niemann-Pick disease, type C1

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

Toward Early Diagnosis and Therapeutic Discovery in CLN3 Disease: A Computational Biomarker Discovery Framework

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

Molecular basis of Salla Disease: R39C Mutation Effects on the Lysosomal Transporter Sialin

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

Development and fit for purpose validation of a quantitative LC-MS/MS method for heparan sulfate in cerebrospinal fluid as a biomarker for mucopolysaccharidosis type IIIA

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.

Translational lipidomics reveals BMP and its precursor LPG as biomarkers for CLN5 Batten disease

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.

Optimization of systemic AAV9 gene therapy in Niemann-Pick disease type C1 mice

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.

PPa1 insufficiency drives lysosomal storage disease and inflammatory macrophage expansion in the bone marrow.

Distinct lysosomal dysfunction patterns of GRN deficiency in the CNS implicate progranulin in cell type-specific protein sorting

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

Synthetic analogue of adrenocorticotropic hormone, ACTH(4-7)PGP delays neurological manifestations in diseases of mucopolysaccharidosis III spectrum by reducing neuroinflammation and rescuing neurotransmission, synaptogenesis, and axonal demyelination

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.

AAV9 Gene Therapy in GM1 Gangliosidosis Type II: A Phase 1/2 Trial

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

Cell-Type Resolved Protein Atlas of Brain Lysosomes Identifies SLC45A1-Associated Disease as a Lysosomal Disorder

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.

Repurposing the HMG-CoA Reductase Inhibitor Atorvastatin for SRD5A3-CDG

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

Cathepsin-dependent amyloid formation drives mechanical rupture of lysosomal membranes

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

GBA1 deficiency differentially affects endolysosomal trafficking in neurons versus astrocytes

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.

Enteric nervous system degeneration in human and murine CLN3 disease, is ameliorated by gene therapy in mice

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.

A stuttering-associated Gnptab variant alters fine-motor kinematics

This study shows that a Gnptab variant impairs fine motor skills in mice by affecting grasp shaping and trajectory control.