TL;DR
A transcriptional framework linking early TDP-43 stress responses to pathological aggregation in AD is provided, and potential upstream therapeutic targets are revealed, including ERK1/2, PI3K, small GTPases, and mRNA splicing pathways.
Key features of mitochondrial homeostasis in neurons are outlined, neuropathological and clinical data supporting the relevance of TDP-43 in AD are reviewed, and emerging mechanisms by which TDP-43 may perturb mitochondrial homeostasis are synthesized.
New models with inactivating mutations in the nuclear localization sequence of TDP-43 are generated and phosphorylation-mediated neurotoxicity of both cytoplasmic and nuclear localized TDP-43 is controlled by the phosphatase calcineurin.
Current evidence on the RNA regulatory networks in PD is examined, highlighting the role of transcript isoforms and RBPs in neuronal dysfunction and emerging data suggest that dysregulation of RNA binding proteins (RBPs) may influence RNA processing in PD.
New mechanistic truths of how m6A-dependent RNA regulation contributes to the progression of AD are compiled and therapeutic opportunities of METTL3/IGF2BP2 axis targeting for novel RNA-based therapies for neurodegenerative disease are discussed.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by synaptic dysfunction, protein aggregation, and widespread molecular alterations in the brain. In this study, we applied quantitative mass spectrometry-based proteomics and phosphoproteomics to characterize synaptosomes and sarkosyl-in...
A novel PIAS1-GSK3β signaling axis in tauopathy and a cell-permeable blocking peptide designed to disrupt the PIAS1-GSK3β interaction are uncovered and provide a promising targeted therapeutic strategy for Alzheimer's disease.
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