Reaction to Endoplasmic Reticulum Stress ATF6 in Amyotrophic Lateral Sclerosis Deteriorates With Aging.

Amyotrophic lateral sclerosis (ALS) is a multisystemic neurodegenerative disorder. Given that peripheral blood mononuclear cells (PBMCs) serve as a "window to the central nervous system" we aimed to answer whether endoplasmic reticulum (ER) stress in ALS-PBMCs is related to disease aggressiveness. We studied ER stress in the PBMCs of 49 patients with ALS and 31 age- and sex-matched healthy controls.

Investigation of mitochondrial calcium uniporter role in embryonic and adult motor neurons from G93A mice.

Amyotrophic lateral sclerosis is characterized by progressive death of motor neurons (MNs) with glutamate excitotoxicity and mitochondrial Ca overload as critical mechanisms in disease pathophysiology. We used MNs from G93A and nontransgenic embryonic cultures and adult mice to analyze the expression of the main mitochondrial calcium uniporter (MCU). MCU was overexpressed in cultured embryonic G93A MNs compared to nontransgenic MNs but downregulated in MNs from adult G93A mice.

Interferon-γ Receptor 1 and GluR1 upregulated in motor neurons of symptomatic hSOD1G93A mice.

Motor neurons are markedly vulnerable to excitotoxicity mostly by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor (AMPAR) stimulation and are principal targets in the neurodegenerative disease Amyotrophic Lateral Sclerosis. Interferon-gamma (IFN-γ), a pro-inflammatory cytokine, can independently cause neuronal dysfunction by triggering calcium influx through a calcium-permeable complex of IFN-γ receptor 1(IFNGR1) subunit and AMPAR subunit GluR1. This receptor complex is formed via a non-canonical neuron-specific IFN-γ pathway that involves Jak1/Stat1 and Protein Kinase A.

DNA strand breaks and TDP-43 mislocation are absent in the murine hSOD1G93A model of amyotrophic lateral sclerosis in vivo and in vitro.

Mutations in the human Cu/Zn superoxide dismutase type-1 (hSOD1) gene are common in familial amyotrophic lateral sclerosis (fALS). The pathophysiology has been linked to, e.g.

Sigma 1 receptor activation modifies intracellular calcium exchange in the G93A ALS model.

Aberrations in intracellular calcium (Ca) have been well established within amyotrophic lateral sclerosis (ALS), a severe motor neuron disease. Intracellular Ca concentration is controlled in part through the endoplasmic reticulum (ER) mitochondria Ca cycle (ERMCC). The ER supplies Ca to the mitochondria at close contacts between the two organelles, i.

Down-regulation of purinergic P2X7 receptor expression and intracellular calcium dysregulation in peripheral blood mononuclear cells of patients with amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated with intracellular Ca(2+) dysregulation. The P2X receptor family is comprised of ligand-gated ion channels that respond to extracellular adenosine triphosphate (ATP) and increases permeability of calcium into the cell. The underlying mechanisms of purinergic signalling on peripheral blood mononuclear cells (PBMCs) in ALS remain unclear.

Novel computer vision algorithm for the reliable analysis of organelle morphology in whole cell 3D images--A pilot study for the quantitative evaluation of mitochondrial fragmentation in amyotrophic lateral sclerosis.

The function of intact organelles, whether mitochondria, Golgi apparatus or endoplasmic reticulum (ER), relies on their proper morphological organization. It is recognized that disturbances of organelle morphology are early events in disease manifestation, but reliable and quantitative detection of organelle morphology is difficult and time-consuming. Here we present a novel computer vision algorithm for the assessment of organelle morphology in whole cell 3D images.

The ER mitochondria calcium cycle and ER stress response as therapeutic targets in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. Although the etiology remains unclear, disturbances in calcium homoeostasis and protein folding are essential features of neurodegeneration in this disorder. Here, we review recent research findings on the interaction between endoplasmic reticulum (ER) and mitochondria, and its effect on calcium signaling and oxidative stress.