After many years of testing different monoclonal antibodies against amyloid-β protein, the results obtained are far from being outstanding, and the control of the progression and symptoms of Alzheimer’s disease (AD) remains elusive. At the recent AD/PD 2024 conference held in Lisbon, new non-anti-amyloidogenic strategies in the starting line against AD were discussed. Professor Einar Sigurdsson from New York University gave a presentation entitled, “Single domain antibodies for therapy and diagnosis of synucleinopathies and tauopathies.”
After many years of testing different monoclonal antibodies against amyloid-β protein, the results obtained are far from being outstanding, and the control of the progression and symptoms of Alzheimer’s disease (AD) remains elusive. At the recent AD/PD 2024 conference held in Lisbon, new non-anti-amyloidogenic strategies in the starting line against AD were discussed. Professor Einar Sigurdsson from New York University gave a presentation entitled, “Single domain antibodies for therapy and diagnosis of synucleinopathies and tauopathies.”
REV-ERBα (NR1D1) is a circadian transcriptional repressor that plays a role in the regulation of lipid metabolism and macrophage function, and the global deletion of REV-ERBα has been previously linked to increased microglial activation and mitigation of amyloid plaque formation. In the current study, researchers from Washington University in St Louis and affiliated organizations aimed to explore the cell-autonomous effects of microglial REV-ERBα on tau pathology.
Dominantly inherited mutations in the MAPT gene, which encodes the tau protein, result in a subset of tauopathies named frontotemporal lobar degeneration with tau pathology (FTLD-tau). However, the mechanisms by which MAPT mutations cause disease remain unclear. In a recent study, researchers from Washington University in St. Louis aimed to investigate the role of long non-coding RNAs (lncRNAs) and the impact of MAPT mutations on lncRNA in tauopathy.
Protein quality control research is “almost exclusively focused on heat shock proteins, which are ubiquitously present” up and down the evolutionary chain, Xiaolu Yang told BioWorld. But “for more sophisticated organisms, which we humans like to think we are, it’s a little odd that we still use the system that bacteria started with…. It seems like we should have something more. The TRIM system,” he added, “fills that gap.”
Protein quality control research is “almost exclusively focused on heat shock proteins, which are ubiquitously present” up and down the evolutionary chain, Xiaolu Yang told BioWorld. But “for more sophisticated organisms, which we humans like to think we are, it’s a little odd that we still use the system that bacteria started with…. It seems like we should have something more. The TRIM system,” he added, “fills that gap.”
TRIMs or tripartite motif proteins are a group of quality control proteins that are found only in animals. One of their functions is to add ubiquitin tags to proteins, marking them for transport to the proteasome system. TRIMs are part of the innate antiviral defense system. But in the July 27, 2023, issue of Science, Yang, who is a professor of cancer biology in the Perelman School of Medicine at the University of Pennsylvania, and his colleagues reported that TRIM11 interacts with tau protein in multiple ways that were beneficial in preventing tauopathies.
Researchers from Arizona State University presented preclinical data for the novel dual specificity tyrosine phosphorylation kinase 1a (DYRK1a) inhibitor DYR-533, being developed for the treatment of tauopathies, including Alzheimer’s disease (AD).
The inhibition of an enzyme associated with neurodegeneration processes reduced the toxic effect of tau, one of the proteins that damage neurons in Alzheimer’s disease (AD). A group of scientists from the University of Helsinki have shown in vitro and in animal models of AD how inhibition of the prolyl endopeptidase (PREP) enzyme reduced tau protein aggregations.