A5075871156- Endoplasmic Reticulum Stress and Disease
- Heat shock proteins research
- Hereditary Neurological Disorders
- Genetic Neurodegenerative Diseases
- Muscle Physiology and Disorders
- Neuroblastoma Research and Treatments
- Neurofibromatosis and Schwannoma Cases
- Mitochondrial Function and Pathology
- Toxin Mechanisms and Immunotoxins
- Autophagy in Disease and Therapy
- Meningioma and schwannoma management
- Nerve injury and regeneration
- Cellular Mechanics and Interactions
- Nuclear Receptors and Signaling
University of Antwerp
2020-2025
Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol
2019
Centro de Investigación Biomédica en Red de Cáncer
2019
Each protein must be synthesized with the correct amino acid sequence, folded into its native structure, and transported to a relevant subcellular location complex. If any of these steps fail, cell has capacity break down aberrant proteins maintain homeostasis (also called proteostasis). All cells possess set well-characterized quality control systems minimize misfolding damage it might cause. Autophagy, conserved pathway for degradation long-lived proteins, aggregates, damaged organelles,...
Mitochondria are complex organelles with different compartments, each harbouring their own protein quality control factors. While chaperones of the mitochondrial matrix well characterized, it is poorly understood which protect intermembrane space. Here we show that cytosolic small heat shock proteins imported under basal conditions into space, where they operate as molecular chaperones. Protein misfolding in space leads to increased recruitment proteins. Depletion swelling and reduced...
ABSTRACT Background Missense mutations in the HSPB8 gene, encoding small heat shock protein B8, cause distal hereditary motor neuropathy (dHMN) or an axonal form of Charcot–Marie–Tooth disease (CMT subtype 2L). Mice expressing mutant Hspb8 (Lys141Asn) mimic human disease, whereas mice lacking show no overt phenotype. We aimed to design RNA interference treatment strategy that rescues neuronal and muscle phenotype patient‐derived neurons a knock‐in mouse model CMT2L/dHMN. Methods optimized...
Molecular markers scalable for clinical use are critical the development of effective treatments and design trials. Here, we identify proteins in sera patients mouse models with Charcot-Marie-Tooth disease (CMT) characteristics that make them suitable as biomarkers practice therapeutic We collected serum from CMT1A (C61 het), CMT2D (GarsC201R, GarsP278KY), CMT1X (Gjb1-null), CMT2L (Hspb8K141N) CMT genotypes including (PMP22d), (GARS), CMT2N (AARS) other rare genetic forms CMT. The severity...
Chaperone-assisted selective autophagy (CASA) is a highly pathway for the disposal of misfolding and aggregating proteins. In muscle, CASA assures muscle integrity by favoring turnover structural components damaged mechanical strain. neurons, promotes removal substrates. A crucial player HSPB8 (heat shock protein family B (small) member 8), which acts in complex with HSPA, their cochaperone BAG3, E3 ubiquitin ligase STUB1. Recently, four novel frameshift (fs) gene mutations have been linked...
Charcot-Marie-Tooth disease is the most common inherited disorder of PNS. CMT1A accounts for 40-50% all cases and caused by a duplication PMP22 gene on chromosome 17, leading to dysmyelination in Patient-derived models study such myelination defects are lacking as vitro generation human myelinating Schwann cells has proved be particularly challenging. Here, we present an induced pluripotent stem cell-derived organoid culture, containing various cell types PNS, including cells, which mimics...