- Alzheimer's disease research and treatments
- Genetics, Aging, and Longevity in Model Organisms
- Bacterial biofilms and quorum sensing
- RNA Research and Splicing
- Cerebrovascular and genetic disorders
- RNA Interference and Gene Delivery
- Prion Diseases and Protein Misfolding
- Amyotrophic Lateral Sclerosis Research
- Heat shock proteins research
- Antimicrobial Peptides and Activities
- Virus-based gene therapy research
- Cancer Research and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Biochemical and Structural Characterization
- Immunotherapy and Immune Responses
- Parkinson's Disease Mechanisms and Treatments
- Protein Structure and Dynamics
Washington University in St. Louis
2019-2024
Abstract Parkinson’s disease (PD) is closely linked to α-synuclein (α-syn) misfolding and accumulation in Lewy bodies. The PDZ serine protease HTRA1 degrades fibrillar tau, which associated with Alzheimer’s disease, inactivating mutations mitochondrial HTRA2 are implicated PD. Here, we report that inhibits aggregation of α-syn as well FUS TDP-43, amyotrophic lateral sclerosis (ALS) frontotemporal dementia. domain necessary sufficient for inhibiting aggregation, yet this activity...
De novo designed peptides that self-assemble into cross-β rich fibrillar biomaterials have been pursued as an innovative platform for the development of adjuvant- and inflammation-free vaccines. However, they share structural morphological properties similar to amyloid species implicated in neurodegenerative diseases, which has a long-standing concern their successful translation. Here, we comprehensively characterize amyloidogenic character amphipathic self-assembling peptide KFE8, compared...
Hsp104, a yeast protein disaggregase, can be potentiated via numerous missense mutations at disparate locations throughout the coiled-coil middle domain (MD). Potentiated Hsp104 variants counter toxicity and misfolding of TDP-43, FUS, α-synuclein, proteins which are implicated in neurodegenerative disorders. However, MD typically exhibit off-target toxicity. Further, it has remained confounding how degenerate confer potentiation, hampering engineering therapeutic variants. Here, we sought to...
ABSTRACT Phenol-soluble modulins (PSMs) are the primary proteinaceous component of Staphylococcus aureus biofilms. Residence in protective environment biofilms allows bacteria to rapidly evolve and acquire antimicrobial resistance, which can lead persistent infections such as those caused by methicillin-resistant S. (MRSA). In their soluble form, PSMs hinder immune response host increase virulence potential MRSA. also self-assemble into insoluble functional amyloids that contribute...