AI Article Synopsis
- Lysosomal storage diseases (LSDs) present serious systemic and central nervous system symptoms, with current treatments offering limited effectiveness, particularly for neurological issues.
- Recent research shows that recombinant human heat shock protein 70 (HSP70) enhances the function of sphingolipid-degrading enzymes and reverses lysosomal damage in cells from patients with various LSDs.
- HSP70 also improves conditions in animal models of LSDs by reducing harmful lipid accumulation and alleviating neurological symptoms, indicating potential for heat shock protein therapies in clinical settings.
Article Abstract
Lysosomal storage diseases (LSDs) often manifest with severe systemic and central nervous system (CNS) symptoms. The existing treatment options are limited and have no or only modest efficacy against neurological manifestations of disease. We demonstrate that recombinant human heat shock protein 70 (HSP70) improves the binding of several sphingolipid-degrading enzymes to their essential cofactor bis(monoacyl)glycerophosphate in vitro. HSP70 treatment reversed lysosomal pathology in primary fibroblasts from 14 patients with eight different LSDs. HSP70 penetrated effectively into murine tissues including the CNS and inhibited glycosphingolipid accumulation in murine models of Fabry disease (Gla(-/-)), Sandhoff disease (Hexb(-/-)), and Niemann-Pick disease type C (Npc1(-/-)) and attenuated a wide spectrum of disease-associated neurological symptoms in Hexb(-/-) and Npc1(-/-) mice. Oral administration of arimoclomol, a small-molecule coinducer of HSPs that is currently in clinical trials for Niemann-Pick disease type C (NPC), recapitulated the effects of recombinant human HSP70, suggesting that heat shock protein-based therapies merit clinical evaluation for treating LSDs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821533 | PMC |
| http://dx.doi.org/10.1126/scitranslmed.aad9823 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A nanoparticle-based wireless deep brain stimulation system that reverses Parkinson's disease.
Sci Adv
January 2025
New Cornerstone Science Laboratory, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.
Deep brain stimulation technology enables the neural modulation with precise spatial control but requires permanent implantation of conduits. Here, we describe a photothermal wireless deep brain stimulation nanosystem capable of eliminating α-synuclein aggregates and restoring degenerated dopamine neurons in the substantia nigra to treat Parkinson's disease. This nanosystem (ATB NPs) consists of gold nanoshell, an antibody against the heat-sensitive transient receptor potential vanilloid family member 1 (TRPV1), and β-synuclein (β-syn) peptides with a near infrared-responsive linker.
View Article and Find Full Text PDFPristimerin Promotes Ubiquitination of HSPA8 and Activates the VAV1/ERK Pathway to Suppress TNBC Proliferation.
Adv Sci (Weinh)
January 2025
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510080, P. R. China.
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis. The natural compound pristimerin has shown promising anti-tumor effect. Here, it is found that pristimerin significantly triggered the activation of autophagy initiation and induced apoptosis in TNBC.
View Article and Find Full Text PDFEffect of administration of nanoparticles of human chorionic gonadotropin on testicular hemodynamics, testicular volume, testicular echotexture, and circulating testosterone and nitric oxide in pubescent goat bucks under heat stress conditions.
Vet Res Commun
January 2025
Department of Theriogenology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
The current study investigated the effect of a single administration of human chorionic gonadotropin hormone (hCG) and its nanoparticles (NPs) on testicular hemodynamics using Doppler ultrasonography, testicular volume, testicular echotexture (PIX), and circulating testosterone and nitric oxide (NO) in pubescent goat bucks during summer months. Fifteen Baladi goats were divided into three groups (5 in each) and subjected to a single intramuscular administration of one ml of physiological saline ( control group), one ml containing 500 IU of hCG (hCG group) or one ml containing 125 IU of hCG NPs (hCG NPs group). Testicular hemodynamics assessment was done just before administration (0 h), and at 2, 4, 6, 24, and daily till 7 days after administration.
View Article and Find Full Text PDFImpact of exogenous rhamnolipids on plant photosynthesis and biochemical parameters under prolonged heat stress.
Photosynthetica
January 2025
University of Reims Champagne-Ardenne, INRAE, RIBP, USC 1488, 51100 Reims, France.
High temperatures severely affect plant growth and development leading to major yield losses. These temperatures are expected to increase further due to global warming, with longer and more frequent heat waves. Rhamnolipids (RLs) are known to protect several plants against various pathogens.
View Article and Find Full Text PDFFlow Cytometry Analysis of Perturbations in the Bacterial Cell Envelope Enabled by Monitoring Generalized Polarization of the Solvatochromic Peptide UNR-1.
Anal Chem
January 2025
Laboratoire d'Innovation Thérapeutique, UMR7200 CNRS, Université de Strasbourg, Institut du Médicament de Strasbourg, 74 route du Rhin, Strasbourg F-67000, France.
The worldwide spread of antibiotic resistance is considered to be one of the major health threats to society. While developing new antibiotics is crucial, there is also a strong need for next-generation analytical methods for studying the physiological state of live bacteria in heterogeneous populations and their response to environmental stress. Here we report a single-cell high-throughput method to monitor changes in the bacterial cell envelope in response to stress based on ratiometric flow cytometry.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!