Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The identification of one mechanism that causes vision loss in inherited degenerative retinal disorders revealed a new signaling molecule that represents a potential therapy for these currently untreatable diseases. This protein, called rod-derived cone viability factor (RdCVF), maintains the function and consequently the viability of cone photoreceptor cells in the retina; mice that lack this factor exhibit a progressive loss of photoreceptor cells. The gene encoding RdCVF also encodes, by differential splicing, a second product that has characteristics of a thioredoxin-like enzyme and protects both photoreceptor cells and, more specifically, its interacting protein partner, the tau protein, against oxidative damage. This signaling pathway potentially links environmental insults to an endogenous neuroprotective response.
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PMID:Rod-derived cone viability factor for treating blinding diseases: from clinic to redox signaling. 2037 63

Alzheimer disease (AD) is the most common neurodegenerative disease, but there is currently no effective treatment available because the etiology or mechanism of AD is still unclear. Many neurodegenerative diseases feature inclusions, which contain accumulations of misfolded, aggregated proteins. Amyloid plaques and neurofibrillary tangles (NFTs) are the major pathological hallmarks of AD. NFTs are composed of tubular filaments, and paired helical filaments containing polymerized hyperphosphorylated tau protein. Another feature is excessive generation of nitric oxide synthetase, reactive nitrogen species, and reactive oxygen species. Protein disulfide isomerase (PDI) is a member of the thioredoxin (TX) superfamily and is believed to accelerate the folding of disulfide-bonded proteins by catalyzing the disulfide interchange reaction, which is the rate-limiting step during protein folding in the luminal space of the endoplasmic reticulum (ER). Nitric oxide (NO)-induced S-nitrosylation of PDI inhibits its enzymatic activity, leading to the accumulation of polyubiquitinated proteins, and activates the unfolded protein response in neurodegenerative diseases. In this study, we found NFTs positive for anti-PDI-antibody in the brain of patients with AD. As far as we know, this is the first report of anti-PDI-antibody-immunopositive inclusions in AD. In AD, NO may inhibit PDI by inducing S-nitrosylation, which inhibits its enzymatic activity and thus allows protein misfolding to occur. Consequently, the accumulation of misfolded proteins induces ER stress. The ER stress can cause apoptosis of neuronal cells. These results suggest that PDI could be a therapeutic target to prevent ER stress in neuronal cells in AD.
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PMID:Protein disulfide isomerase-immunopositive inclusions in patients with Alzheimer disease. 2055 Sep 46

Amyloid plaques and neurofibrillary tangles are the major pathological hallmarks of Alzheimer's disease. Neurofibrillary tangles are composed of filaments and paired helical filaments containing polymerized hyperphosphorylated tau protein. Derlin proteins are a family of proteins that are conserved in all eukaryotes, in which they function in endoplasmic reticulum-associated degradation. Protein disulfide isomerase (PDI) is a member of the thioredoxin superfamily and is believed to accelerate the folding of disulfide-bonded proteins in the luminal space of the endoplasmic reticulum. In this study, we found that derlin-1 and PDI were colocalized in neurofibrillary tangles in the brain of patients with Alzheimer's disease. Derlin-1 and PDI may work as partners to avoid the accumulation of unfolded proteins in Alzheimer's disease. Furthermore, we found that derlin-1 was immunopositive for neurofibrillary tangles and upregulated in Alzheimer's disease and that derlin-1 may play an important role in endoplasmic reticulum-associated degradation during the pathogenesis of Alzheimer's disease. We hypothesize that derlin-1 was upregulated to avoid the aggregation of unfolded proteins. Despite the upregulation of derlin-1, the functions of chaperone proteins and Alzheimer tau protein were lost and these proteins were also accumulated. Finally, they were involved in neurofibrillary tangles. These results suggest that derlin-1 may be associated with endoplasmic reticulum stress in neuronal cells in Alzheimer's disease.
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PMID:Derlin-1-immunopositive inclusions in patients with Alzheimer's disease. 2262