Cerebrospinal Fluid and Serum Neuron‐Specific Enolase in Niemann‐Pick Disease Type C1

American Journal of Medical Genetics Part A, Год журнала: 2024, Номер unknown

Опубликована: Дек. 17, 2024

ABSTRACT Niemann‐Pick disease, type C1 (NPC1) is an ultra rare, autosomal recessive disorder characterized by impaired intracellular cholesterol trafficking. This study assessed neuron‐specific enolase (NSE) as a biomarker for disease status and treatment response in individuals with NPC1. We also evaluated the concordance between serum cerebrospinal fluid (CSF) NSE measurements. A total of 34 NPC1 were included this analysis. Overall, 10 participants used to compare concurrent samples CSF NSE. levels correlated indexes severity (Annual Severity Increment Score [ASIS] age neurological onset) burden (NPC Neurological [NSS]). was elevated CSF, but paired CSF/serum not ( r s = −0.16, p 0.64). Additionally, no significant correlations observed clinical measures either or severity. values showed positive association ASIS 0.37, 0.0291) onset NPC NSSs. Longitudinal analysis nine 0.0317) decrease after initiation intrathecal 2‐hydroxypropyl‐β‐cyclodextrin (IT HPβCD) therapy. suggests that may have some utility therapeutic trials.

Язык: Английский

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Circadian Influences on Brain Lipid Metabolism and Neurodegenerative Diseases

Metabolites, Год журнала: 2024, Номер 14(12), С. 723 - 723

Опубликована: Дек. 22, 2024

Circadian rhythms are intrinsic, 24 h cycles that regulate key physiological, mental, and behavioral processes, including sleep–wake cycles, hormone secretion, metabolism. These controlled by the brain’s suprachiasmatic nucleus, which synchronizes with environmental signals, such as light temperature, consequently maintains alignment day–night cycle. Molecular feedback loops, driven core circadian “clock genes”, Clock, Bmal1, Per, Cry, essential for rhythmic gene expression; disruptions in these loops associated various health issues. Dysregulated lipid metabolism brain has been implicated pathogenesis of neurological disorders contributing to oxidative stress, neuroinflammation, synaptic dysfunction, observed conditions Alzheimer’s Parkinson’s diseases. Disruptions expression have shown perturb regulatory mechanisms brain, thereby triggering neuroinflammatory responses damage. This review synthesizes current insights into interconnections between metabolism, a focus on their roles disease. It further examines how desynchronization genes affects explores potential through disrupted signaling might contribute pathophysiology neurodegenerative disorders.

Язык: Английский

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Development and validation of a new genotype–phenotype correlation for Niemann‐Pick disease type C1

Journal of Inherited Metabolic Disease, Год журнала: 2023, Номер 47(2), С. 317 - 326

Опубликована: Дек. 22, 2023

Язык: Английский

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MicroRNA Profile, Putative Diagnostic Biomarkers and RNA-Based Therapies in the Inherited Lipid Storage Disease Niemann-Pick Type C

Biomedicines, Год журнала: 2023, Номер 11(10), С. 2615 - 2615

Опубликована: Сен. 23, 2023

Lipids are essential for cellular function and tightly controlled at the transcriptional post-transcriptional levels. Dysregulation of these pathways is associated with vascular diseases, diabetes, cancer, several inherited metabolic disorders. MicroRNAs (miRNAs), in particular, a family gene repressors regulation many genes that encode proteins involved multiple lipid metabolism pathways, thereby influencing their homeostasis. Thus, this class non-coding RNAs (ncRNAs) has emerged as promising therapeutic target treatment lipid-related alterations. Most miRNAs act an intracellular level, but past few years, role intercellular signaling molecules also been uncovered since they can be transported bodily fluids used potential biomarkers In review, we point out current knowledge on miRNA signature lysosomal storage disorder dysfunction, Niemann-Pick type C, discuss use targets RNA-based therapies.

Язык: Английский

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Reversal of pathologic changes in fibroblasts from Niemann-Pick type C disease patients by inhibition of bromodomain and extraterminal proteins

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Дек. 20, 2023

Abstract Niemann-Pick type C disease (NPCD) is a lysosomal disorder whith patients presenting highly variable onset, neurovisceral symptoms and life spans due to defective lipid homeostasis. At present, therapeutic options are limited palliative disease-modifying drugs, there continued need for new approaches. Here, we explored bromodomain extraterminal (BET) proteins as drug target NPCD using patient-derived fibroblasts. Treatment of cells with JQ1, prototype BET inhibitor, enhanced the level NPC1 protein increased its presence in lysosomes, diminished expansion cholesterol accumulation induced extracellular release components time- dose-dependent manner. The reversal pathologic changes an established cell model suggest inhibition approach NPCD.

Язык: Английский

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