Origin of Elevated S-Glutathionylated GAPDH in Chronic Neurodegenerative Diseases.

HO-oxidized glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalytic cysteine residues (C(SH) undergo rapid S-glutathionylation. Restoration of the enzyme activity is accomplished by thiol/disulfide S2 displacement (directly or enzymatically) forming glutathione disulfide (G(SS)G) and active enzyme, a process that should be facile as C(SH) reside on the subunit surface. As S-glutathionylated GAPDH accumulates following ischemic and/or oxidative stress, in vitro/silico approaches have been employed to address this paradox.

Mechanism of GAPDH Redox Signaling by HO Activation of a Two-Cysteine Switch.

Oxidation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by reactive oxygen species such as HO activate pleiotropic signaling pathways is associated with pathophysiological cell fate decisions. Oxidized GAPDH binds chaperone proteins with translocation of the complex to the nucleus and mitochondria initiating autophagy and cellular apoptosis. In this study, we establish the mechanism by which HO-oxidized GAPDH subunits undergo a subunit conformational rearrangement.

Antiphospholipid autoantibodies as blood biomarkers for detection of early stage Alzheimer's disease.

A robust blood biomarker is urgently needed to facilitate early prognosis for those at risk for Alzheimer's disease (AD). Redox reactive autoantibodies (R-RAAs) represent a novel family of antibodies detectable only after exposure of cerebrospinal fluid (CSF), serum, plasma or immunoglobulin fractions to oxidizing agents. We have previously reported that R-RAA antiphospholipid antibodies (aPLs) are significantly decreased in the CSF and serum of AD patients compared to healthy controls (HCs).

Factors responsible for neurofibrillary tangles and neuronal cell losses in tauopathy.

TgTauP301L mice that overexpress the mutant human tauP301L present in FTDP-17 reproduce neurofibrillary tangles (NFTs), neuronal cell losses, memory disturbance, and substantial phenotypic variation. To demonstrate factors responsible for NFT formation and neuronal cell losses, sets of TgTauP301L for comparison with or without NFTs and neuronal cell losses were studied with oligonucleotide microarrays. Gene expressions were altered in biological pathways, including oxidative stress, apoptosis, mitochondrial fatty acid betaoxidation, inflammatory response pathway, and complement and coagulation cascade pathways.