Neuroscience
- Biallelic ADPRHL2 mutations in complex neuropathy affect ADP ribosylation and DNA damage response
This 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 system
In 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 mice
This 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 remodelling
Endolysosomes 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 simulations
Cryo-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 necrosis
DNA 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 vivo
Exogenous 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 responses
Progranulin 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.
- Non-microtubule tubulin-based backbone and subordinate components of postsynaptic density lattices
This study proposes a postsynaptic density (PSD) lattice model comprising a non-microtubule tubulin-based backbone structure and its associated proteins, including various PSD scaffold/adaptor proteins and other PSD proteins.
- Concomitant gain and loss of function pathomechanisms in C9ORF72 amyotrophic lateral sclerosis
Axonal trafficking deficits and neurodegeneration in C9ORF72 motoneurons are mediated by GOF and LOF mechanisms with RNA foci and DPRs as upstream events, whereas DNA damage appears downstream.