A drug-like molecule called ISRIB, which activates the translation initiation factor eIF2B, antagonizes stress responses as diverse as protein misfolding and nutrient deprivation, and restores protein synthesis, enhancing memory.
The combination of optical diffraction tomography and Brillouin microscopy in a single setup enables to quantitatively map the viscoelastic properties of cellular compartments such as aggregates and stress granules in vivo.
Jonathan Gilley, Oscar Jackson ... Michael P Coleman
Rare SARM1 alleles encoding SARM1 variants that have constitutively high NADase activity and sensitise cultured neurons to mild stress are risk alleles for ALS and other, related motor disorders.
Lindsey R Hayes, Lauren Duan ... Jeffrey D Rothstein
Poly-PR and poly-GR interact with importin β, disrupt importin-cargo loading, and inhibit nuclear import in permeabilized cells in a manner that can be rescued by RNA.
Preventing activity of the kinase tumor progression locus 2 modulates microglial activation, reduces T-cell brain infiltration, and is neuroprotective in disease models.
In neuronal mitophagy, Parkin and OPTN induce efficient sequestration of damaged somal mitochondria into autophagosomes, but slow turnover via lysosomal acidification may be a point of vulnerability for the cell.
An image-based multiplex autophagosome RNAi screen targeting all Rab GTPases as well as their GAPs and GEFs identifies the Rab GEF SMCR8 as multifaceted autophagy modulator, which regulates kinase activity and gene expression of ULK1.