Single-session reproducibility of MR spectroscopy measures of glutathione in the mesial temporal lobe with MEGA-PRESS.

Background And Purpose: Magnetic resonance spectroscopy (MRS) measures neurochemicals in vivo. Glutathione (GSH) is a neuroprotective chemical shown to vary significantly in patients with Alzheimer's disease (AD). This work investigates the reproducibility of GSH measures in the mesial temporal lobe (MTL) to identify its potential clinical utility.

A biosensor of protein foldedness identifies increased "holdase" activity of chaperones in the nucleus following increased cytosolic protein aggregation.

Chaperones and other quality control machinery guard proteins from inappropriate aggregation, which is a hallmark of neurodegenerative diseases. However, how the systems that regulate the "foldedness" of the proteome remain buffered under stress conditions and in different cellular compartments remains incompletely understood. In this study, we applied a FRET-based strategy to explore how well quality control machinery protects against the misfolding and aggregation of "bait" biosensor proteins, made from the prokaryotic ribonuclease barnase, in the nucleus and cytosol of human embryonic kidney 293T cells.

Severely impaired CTL killing is a feature of the neurological disorder Niemann-Pick disease type C1.

Niemann-Pick disease type C1 (NP-C1) is a rare lysosomal storage disorder resulting from mutations in an endolysosomal cholesterol transporter, NPC1. Despite typically presenting with pronounced neurological manifestations, NP-C1 also resembles long-term congenital immunodeficiencies that arise from impairment of cytotoxic T lymphocyte (CTL) effector function. CTLs kill their targets through exocytosis of the contents of lysosome-like secretory cytotoxic granules (CGs) that store and ultimately release the essential pore-forming protein perforin and proapoptotic serine proteases, granzymes, into the synapse formed between the CTL and target cell.

Changes in ferrous iron and glutathione promote ferroptosis and frailty in aging .

All eukaryotes require iron. Replication, detoxification, and a cancer-protective form of regulated cell death termed , all depend on iron metabolism. Ferrous iron accumulates over adult lifetime in .

Author Correction: Imaging tau and amyloid-β proteinopathies in Alzheimer disease and other conditions.

In Figure 1 of this article as originally published, the chemical structure at bottom right was incorrectly labelled F-PM-PBB3. The text label has been corrected to F-PBB3 in the PDF and HTML versions of the article. As of this date, the structure of PM-PBB3 (also known as APN-1607) has not yet been published.

Imaging tau and amyloid-β proteinopathies in Alzheimer disease and other conditions.

Most neurodegenerative disorders are associated with aggregated protein deposits. In the case of Alzheimer disease (AD), extracellular amyloid-β (Aβ) aggregates and intracellular tau neurofibrillary tangles are the two neuropathological hallmarks of the disease. Aβ-PET imaging has already been approved for clinical use and is being used in clinical trials of anti-Aβ therapies both for patient recruitment and as an outcome measure.