A5015180743- Heat shock proteins research
- Endoplasmic Reticulum Stress and Disease
- Amyotrophic Lateral Sclerosis Research
- RNA Research and Splicing
- Autophagy in Disease and Therapy
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Muscle Physiology and Disorders
- Fibromyalgia and Chronic Fatigue Syndrome Research
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Genetics, Aging, and Longevity in Model Organisms
- Nuclear Structure and Function
- RNA modifications and cancer
- Exercise and Physiological Responses
- Cardiomyopathy and Myosin Studies
- Parkinson's Disease Mechanisms and Treatments
- Hereditary Neurological Disorders
- Prion Diseases and Protein Misfolding
- Spaceflight effects on biology
- Connective tissue disorders research
- Protein Structure and Dynamics
- Signaling Pathways in Disease
- Mitochondrial Function and Pathology
- thermodynamics and calorimetric analyses
University of Modena and Reggio Emilia
2016-2025
Center for Systems Biology Dresden
2023
Technische Universität Dresden
2023
University Hospital Carl Gustav Carus
2023
University Medical Center Groningen
2008-2017
University of Groningen
2008-2017
Azienda Ospedaliera Carlo Poma
2015
Dialyse Centrum Groningen
2014
Université Laval
2005-2010
Hôtel-Dieu de Québec
2005
Article4 April 2017Open Access Transparent process An aberrant phase transition of stress granules triggered by misfolded protein and prevented chaperone function Daniel Mateju Max Planck Institute Molecular Cell Biology Genetics, Dresden, Germany Search for more papers this author Titus M Franzmann Avinash Patel Andrii Kopach Edgar E Boczek Shovamayee Maharana Hyun O Lee Serena Carra Department Biomedical, Metabolic Neural Sciences, University Modena Reggio Emilia, Modena, Italy Anthony A...
Mutations in HspB8, a member of the B group heat shock proteins (Hsp), have been associated with human neuromuscular disorders. However, exact function HspB8 is not yet clear. We previously demonstrated that overexpression cultured cells prevents accumulation aggregation-prone such as polyglutamine protein Htt43Q. Here we report forms stable complex Bag3 and formation this essential for activity HspB8. resulted accelerated degradation Htt43Q, whereas knockdown prevented HspB8-induced Htt43Q...
Several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), are characterized by the presence of misfolded proteins, thought to trigger neurotoxicity. Some familial forms ALS (fALS), clinically indistinguishable from sporadic (sALS), linked superoxide dismutase 1 (SOD1) gene mutations. It has been shown that mutant SOD1 misfolds, insoluble aggregates and impairs proteasome. Using transgenic G93A-SOD1 mice, we found spinal cord motor neurons, accumulating also...
The molecular chaperone HspB8 [Hsp (heat-shock protein) B8] is member of the B-group Hsps. These proteins bind to unfolded or misfolded and protect them from aggregation. has been reported form a stable complex with cohort protein Bag3 (Bcl-2-associated athanogene 3). In present study we identify binding regions in crucial for their interaction. We evidence that binds through hydrophobic groove formed by its strands beta4 beta8, region previously known be responsible formation stability...
Stress granules (SGs) are mRNA-protein aggregates induced during stress, which accumulate in many neurodegenerative diseases. Previously, the autophagy-lysosome pathway and valosin-containing protein (VCP), key players of quality control (PQC), were shown to regulate SG degradation. This is consistent with idea that PQC may survey and/or assist dynamics. However, despite these observations, it currently unknown whether actively participates assembly. Here, we describe inhibition autophagy,...
A small number of heat-shock proteins have previously been shown to act protectively on aggregation several containing an extended polyglutamine (polyQ) stretch, which are linked a variety neurodegenerative diseases. specific subfamily is formed by the HSPB family molecular chaperones, comprises 10 members (HSPB1-10, also called HSP). Several them known as anti-aggregation in vitro. Whether they cells against polyQ has so far only studied for few (e.g. HSPB1, HSPB5 and HSPB8). Here, we...
Eukaryotic cells use autophagy and the ubiquitin–proteasome system as their major protein degradation pathways. Upon proteasomal impairment, switch to ensure proper clearance of clients (the proteasome-to-autophagy switch). The HSPA8 HSPA1A cochaperone BAG3 has been suggested be involved in this switch. However, at present it is still unknown whether what extent can indeed reroute autophagosomal pathway. Here, we show that induces sequestration ubiquitinated into cytoplasmic puncta colabeled...
Abstract Neurodegenerative diseases (NDs) are often associated with the presence of misfolded protein inclusions. The chaperone HSPB8 is upregulated in mice, human brain and muscle structures affected during NDs progression. exerts a potent pro-degradative activity on several proteins responsible for familial forms. Here, we demonstrated that also counteracts accumulation aberrantly localized forms TDP-43 its 25 KDa fragment involved most sporadic cases Amyotrophic Lateral Sclerosis (sALS)...
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two neurodegenerative diseases in which similar pathogenic mechanisms involved. Both associate to the high propensity of specific misfolded proteins, like TDP-43 or FUS, mislocalize aggregate. This is partly due their intrinsic biophysical properties as a consequence failure neuronal protein quality control (PQC) system. Several familial ALS/FTD cases linked an expansion repeated G4C2 hexanucleotide sequence present...
Nuclear protein aggregation has been linked to genome instability and disease. The main source of aggregation-prone proteins in cells is defective ribosomal products (DRiPs), which are generated by translating ribosomes the cytoplasm. Here, we report that DRiPs rapidly diffuse into nucleus accumulate nucleoli PML bodies, two membraneless organelles formed liquid-liquid phase separation. We show bodies act as dynamic overflow compartments recruit quality control factors store for later...
Abstract The sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific. Yet, organization system across physiological human tissues has received little attention. Through computational analyses large-scale tissue transcriptomes, we unveil that is composed core elements are uniformly expressed tissues, and variable differentially fit with tissue-specific requirements. We demonstrate via a proteomic analysis muscle-specific signature functional...
Aberrant liquid-to-solid phase transitions of biomolecular condensates have been linked to various neurodegenerative diseases. However, the underlying molecular interactions that drive aging remain enigmatic. Here, we develop quantitative time-resolved crosslinking mass spectrometry monitor protein and dynamics inside formed by fused in sarcoma (FUS). We identify misfolding RNA recognition motif FUS as a key driver condensate aging. demonstrate small heat shock HspB8 partitions into via its...
Article19 March 2021Open Access Source DataTransparent process Hsp90-mediated regulation of DYRK3 couples stress granule disassembly and growth via mTORC1 signaling Laura Mediani Department Biomedical, Metabolic Neural Sciences, Centre for Neuroscience Nanotechnology, University Modena Reggio Emilia, Modena, Italy Search more papers by this author Francesco Antoniani ItalyThese authors are contributed equally to work as second, third Veronica Galli Jonathan Vinet Genomic Post-Genomic Center,...
Cytosolic aggregation of the RNA binding protein TDP-43 (transactive response DNA-binding 43) is a hallmark amyotrophic lateral sclerosis and frontotemporal dementia. Here, we report that during oxidative stress, becomes SUMO2/3-ylated by SUMO E3 ligase PIAS4 (protein inhibitor activated STAT 4) enriches in cytoplasmic stress granules (SGs). Upon pharmacological inhibition SUMO2/3-ylation or depletion, enrichment SGs accompanied irreversible aggregation. In cells are unable to assemble SGs,...
The family of small heat shock proteins (sHsp) is composed 10 members in mammals, four which are found mutated diseases associated with the accumulation protein aggregates. Though many sHsp have demonstrated molecular chaperone activity vitro cell-free conditions, their vivo normal cellular context remains unclear. In present study, we investigated capacity sHsp, HspB8/Hsp22, to prevent aggregation cells using polyglutamine Htt43Q as a model. control accumulated perinuclear inclusions...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons. As with other age-dependent disorders, ALS linked to presence misfolded proteins that may perturb several intracellular mechanisms trigger neurotoxicity. Misfolded aggregate intracellularly generating insoluble inclusions are key neuropathological hallmark ALS. Proteins involved in degradative systems, signaling pathways human TAR DNA-binding...