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Full-Text Articles in Life Sciences
The Nuclear Import Receptor Kapβ2 Modifies Neurotoxicity Mediated By Poly(Gr) In C9orf72-Linked Als/Ftd, Maria Elena Cicardi, V. Kankate, Sindhu Sriramoji, Karthik Krishnamurthy, S. S. Markandaiah, B. M. Verdone, Amandeep Girdhar, A. Nelson, L. B. Rivas, A. Boehringer, Aaron R. Haeusler, Piera Pasinelli, Lin Guo, Davide Trotti
The Nuclear Import Receptor Kapβ2 Modifies Neurotoxicity Mediated By Poly(Gr) In C9orf72-Linked Als/Ftd, Maria Elena Cicardi, V. Kankate, Sindhu Sriramoji, Karthik Krishnamurthy, S. S. Markandaiah, B. M. Verdone, Amandeep Girdhar, A. Nelson, L. B. Rivas, A. Boehringer, Aaron R. Haeusler, Piera Pasinelli, Lin Guo, Davide Trotti
Farber Institute for Neuroscience Faculty Papers
Expanded intronic G4C2 repeats in the C9ORF72 gene cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These intronic repeats are translated through a non-AUG-dependent mechanism into five different dipeptide repeat proteins (DPRs), including poly-glycine-arginine (GR), which is aggregation-prone and neurotoxic. Here, we report that Kapβ2 and GR interact, co-aggregating, in cultured neurons in-vitro and CNS tissue in-vivo. Importantly, this interaction significantly decreased the risk of death of cultured GR-expressing neurons. Downregulation of Kapβ2 is detrimental to their survival, whereas increased Kapβ2 levels mitigated GR-mediated neurotoxicity. As expected, GR-expressing neurons displayed TDP-43 nuclear loss. Raising Kapβ2 levels …
Jun Upregulation Drives Aberrant Transposable Element Mobilization, Associated Innate Immune Response, And Impaired Neurogenesis In Alzheimer’S Disease, Chiara Scopa, Samantha Barnada, Maria Cicardi, Mo Singer, Davide Trotti, Marco Trizzino
Jun Upregulation Drives Aberrant Transposable Element Mobilization, Associated Innate Immune Response, And Impaired Neurogenesis In Alzheimer’S Disease, Chiara Scopa, Samantha Barnada, Maria Cicardi, Mo Singer, Davide Trotti, Marco Trizzino
Farber Institute for Neuroscience Faculty Papers
Adult neurogenic decline, inflammation, and neurodegeneration are phenotypic hallmarks of Alzheimer's disease (AD). Mobilization of transposable elements (TEs) in heterochromatic regions was recently reported in AD, but the underlying mechanisms are still underappreciated. Combining functional genomics with the differentiation of familial and sporadic AD patient derived-iPSCs into hippocampal progenitors, CA3 neurons, and cerebral organoids, we found that the upregulation of the AP-1 subunit, c-Jun, triggers decondensation of genomic regions containing TEs. This leads to the cytoplasmic accumulation of HERVK-derived RNA-DNA hybrids, the activation of the cGAS-STING cascade, and increased levels of cleaved caspase-3, suggesting the initiation of programmed cell death …
Sleep Problems In Old Age: Metabotropic Glutamate Receptor To The Rescue, Sho Inami, Dinis J.S. Afonso, Kyunghee Koh
Sleep Problems In Old Age: Metabotropic Glutamate Receptor To The Rescue, Sho Inami, Dinis J.S. Afonso, Kyunghee Koh
Farber Institute for Neuroscience Faculty Papers
No abstract provided.