Neuroscience
INPP5K and Atlastin-1 maintain the nonuniform distribution of ER–plasma membrane contacts in neuronsCIL-1 and ATLN-1 maintain the balance between ER tubules and sheets and prevent invasion of cortical ER sheets into the axon, contributing to the non-uniform distribution of neuronal ER-PM contacts.
Choroid plexus APP regulates adult brain proliferation and animal behaviorAdult mouse choroid plexus shows elevated APP expression. sAPPα secreted into the CSF modulates neurogenic niche proliferation, whereas choroid plexus expression of fAD APP mutants leads to reduced niche proliferation, deficits in hippocampus synaptic plasticity, and learning defects.
Biallelic ADPRHL2 mutations in complex neuropathy affect ADP ribosylation and DNA damage responseThis work studies known and new ADPRHL2 mutations with different disease mechanisms overall indicating that loss of nuclear ARH3 alone is pathogenic via dysregulated nuclear ADP ribosylation.
Expression of immunoglobulin constant domain genes in neurons of the mouse central nervous systemIn this study, Scheurer et al demonstrate that two genes encoding the effector domain of immunoglobulins are not only expressed by lymphocytes of the immune system but also by neurons in the central nervous system.
Improved systemic AAV gene therapy with a neurotrophic capsid in Niemann–Pick disease type C1 miceThis work highlights the importance of CNS transduction for treatment of neurological diseases, a finding with significant clinical implications considering the long-lasting effects of gene therapy.
Axon terminals control endolysosome diffusion to support synaptic remodellingEndolysosomes present in the presynaptic terminal move by diffusion constrained by F-actin and increase their mobility during the remodelling of synaptic connectivity to support a local degradative activity.
Dynamic closed states of a ligand-gated ion channel captured by cryo-EM and simulationsCryo-EM structures and molecular simulations of a pentameric ligand-gated ion channel, GLIC, in resting and activating conditions implicate protonation sites and altered dynamics in sequential gating.
DNA damage in embryonic neural stem cell determines FTLDs’ fate via early-stage neuronal necrosisDNA damage due to impairment of DNA damage repair functions in NSCs is carried over to neurons and triggers early-stage YAP-dependent neuronal necrosis (TRIAD) amplifying a chain of necrosis in FTLDs.
Microglia show differential transcriptomic response to Aβ peptide aggregates ex vivo and in vivoExogenous amyloid beta peptides cause distinct transcriptomic responses in microglia cultures that are not fully replicated in an amyloid mouse model or identified microglial subpopulations in vivo.
A multifaceted role of progranulin in regulating amyloid-beta dynamics and responsesProgranulin deficiency leads to decreased levels of human APP and Aβ in a sex- and age-dependent manner and enhanced inflammatory and lysosomal responses in the plaque-associated microglia.