Recent Therapeutic Advancements for Gaucher Disease DOI Open Access

Lipi Pradhan,

Sumit Manna,

Pragya Pragya

et al.

Advanced Therapeutics, Journal Year: 2024, Volume and Issue: 8(1)

Published: Nov. 15, 2024

Abstract Gaucher Disease (GD) is a well‐known lysosomal storage disease resulting from mutations in the GBA1 gene. GD exhibits range of clinical manifestations, each with unique symptoms and severity levels. This review explores genetic foundations GD, highlighting significance Glucocerebrosidase (GCase) deficiency, skeletal complications associated such as osteonecrosis, fractures, bone pain, all which significantly negatively influence quality life for patients. Over 700 gene are found to cause variations expression indicating disease's complexity need continued research. Early diagnosis prognosis evaluation depend heavily on diagnostic approaches integrating laboratory assessments, testing, symptoms. Treatment strategies like enzyme replacement therapy (ERT) substrate reduction (SRT) have advanced, but issues high costs invasiveness still exist. focuses novel therapeutic that show promise treating including cell‐based therapies, pharmacological chaperone (PCT), drug delivery via nanoparticles. Finally, discussions current trials, limitations advanced future scope summarized.

Language: Английский

GBA1-Associated Parkinson’s Disease Is a Distinct Entity DOI Open Access
Aliaksandr Skrahin, Mia Horowitz, Majdolen Istaiti

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7102 - 7102

Published: June 28, 2024

-associated Parkinson's disease (

Language: Английский

Citations

4
Comparative analysis of methods for measuring glucocerebrosidase enzyme activity in patients with Parkinson’s disease with the GBA1 variant DOI Creative Commons
Jin Hwangbo, Myung Jun Lee, Sang Jin Kim

et al.

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: April 2, 2025

GBA1 variants are significant genetic risk factors for Parkinson's disease (PD). Accurately measuring glucocerebrosidase (GCase) activity is crucial understanding progression and developing targeted therapies. This study aimed to validate strategies blood GCase in patients with GBA1-associated PD (GBA-PD). We recruited 25 GBA-PD 27 matched without (non-GBA-PD). from fresh was quantified using the 4-methylumbelliferyl β-D-glucopyranoside leukocyte assay (GCaseRaw). The patient/normal control ratio (GCase ratio) calculated consistency. dried spot (DBS) specimens (GCaseDBS) plasma glucosylsphingosine (GluSph) levels were measured LC-MS/MS. diagnostic accuracy assessed area under curve (AUC) values. No differences demographics or characteristics found between non-GBA-PD patients. significantly lower (p < 0.001). exhibited a higher (AUC, 0.93) than GCaseRaw 0.88) GCaseDBS 0.78). Plasma GluSph negatively correlated (r = -0.326; p 0.01). relative of showed strong discriminatory potential, distinguishing non-GBA-PD.

Language: Английский

Citations

0
Investigating the Impact of the Parkinson’s-Associated GBA1 E326K Mutation on β-Glucocerebrosidase Dimerization and Interactome Dynamics Through an In Silico Approach DOI Open Access
Davide Pietrafesa, Alessia Casamassa, Barbara Benassi

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11443 - 11443

Published: Oct. 24, 2024

Heterozygous mutations or genetic variants in the GBA1 gene, which encodes for β-glucocerebrosidase (GCase), a lysosomal hydrolase enzyme, may increase risk of Parkinson’s disease (PD) onset. The heterozygous E326K form is one most common factors PD worldwide, but, to date, underlying molecular mechanisms remain unclear. Here, we investigate effect on structure, stability, dimerization process, and interaction mode with some proteins interactome GCase using multiple dynamics (MD) simulations at pH 5.5 7.0 mimic endoplasmic reticulum environments, respectively. analysis MD trajectories highlights that mutation did not significantly alter structural conformation catalytic dyad but makes structure dimeric complexes unstable, especially pH, potentially impacting organization quaternary structure. Furthermore, impacts protein interactions by altering binding activator Saposin C (SapC), reducing affinity inhibitor α-Synuclein (α-Syn), increasing Lysosomal integral membrane protein-2 (LIMP-2) transporter.

Language: Английский

Citations

0
Recent Therapeutic Advancements for Gaucher Disease DOI Open Access

Lipi Pradhan,

Sumit Manna,

Pragya Pragya

et al.

Advanced Therapeutics, Journal Year: 2024, Volume and Issue: 8(1)

Published: Nov. 15, 2024

Abstract Gaucher Disease (GD) is a well‐known lysosomal storage disease resulting from mutations in the GBA1 gene. GD exhibits range of clinical manifestations, each with unique symptoms and severity levels. This review explores genetic foundations GD, highlighting significance Glucocerebrosidase (GCase) deficiency, skeletal complications associated such as osteonecrosis, fractures, bone pain, all which significantly negatively influence quality life for patients. Over 700 gene are found to cause variations expression indicating disease's complexity need continued research. Early diagnosis prognosis evaluation depend heavily on diagnostic approaches integrating laboratory assessments, testing, symptoms. Treatment strategies like enzyme replacement therapy (ERT) substrate reduction (SRT) have advanced, but issues high costs invasiveness still exist. focuses novel therapeutic that show promise treating including cell‐based therapies, pharmacological chaperone (PCT), drug delivery via nanoparticles. Finally, discussions current trials, limitations advanced future scope summarized.

Language: Английский

Citations

0