p(HBP:"20 S Proteasome")

Entity

Name

20 S Proteasome

Namespace

HBP

Namespace Version

20190126

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/77c0796c3ca82a80cb0eaf1c8380d6ccd7f323af/export/hbp-names.belns

Tau Modifications Sections of NESTOR

A study in cultured mouse neuroblastoma cells showed that N-terminal mutant Huntingtin inhibited the 20S proteasome catalytic activity, in turn causing impaired proteasomal degradation of p53, subsequent loss of mitochondrial membrane potential, release of cytochrome c, caspase activation, and apoptosis (Jana et al., 2001) (Figure 2). PubMed:14556719

In the present study we injected bilaterally 3-morpholino-sydnonimine (SIN-1), a recognized and widely used peroxynitrite donor (25–30), into rat hippocampus, and investigated whether or not peroxynitrite could induce simultaneously nitration and hyperphosphorylation of tau and the underlying mechanisms in vivo. The level of nitrated and hyperphosphorylated tau was markedly increased in rat hippocampus 24 h, and prevented by preinjection of uric acid, a natural scavenger of peroxynitrite. GSK-3beta and p38 MAPKs, including p38alpha, p38beta, and p38delta activity was increased, but no change in the activity of p38gamma, ERK, and c-Jun amino-terminal kinase (JNK). Both nitrated tau and hyperphosphorylated tau were aggregated in the hippocampus, with activity of 20S proteasome significantly arrested in SIN-1-injected rats. Hyperphosphorylated tau was degraded as efficiently as normal tau by 20S proteasome, but the nitrated tau with an unorderly secondary structure became more resistant to the proteolysis, providing evidence that peroxynitrite simultaneously induces tau hyperphosphorylation, nitration, and accumulation, and that activation of GSK-3beta, p38alpha, p38beta, p38delta isoforms and the inhibition of proteasome activity are respectively responsible for the peroxynitrite-induced tau hyperphosphorylation and accumulation. PubMed:16816118

In the present study we injected bilaterally 3-morpholino-sydnonimine (SIN-1), a recognized and widely used peroxynitrite donor (25–30), into rat hippocampus, and investigated whether or not peroxynitrite could induce simultaneously nitration and hyperphosphorylation of tau and the underlying mechanisms in vivo. The level of nitrated and hyperphosphorylated tau was markedly increased in rat hippocampus 24 h, and prevented by preinjection of uric acid, a natural scavenger of peroxynitrite. GSK-3beta and p38 MAPKs, including p38alpha, p38beta, and p38delta activity was increased, but no change in the activity of p38gamma, ERK, and c-Jun amino-terminal kinase (JNK). Both nitrated tau and hyperphosphorylated tau were aggregated in the hippocampus, with activity of 20S proteasome significantly arrested in SIN-1-injected rats. Hyperphosphorylated tau was degraded as efficiently as normal tau by 20S proteasome, but the nitrated tau with an unorderly secondary structure became more resistant to the proteolysis, providing evidence that peroxynitrite simultaneously induces tau hyperphosphorylation, nitration, and accumulation, and that activation of GSK-3beta, p38alpha, p38beta, p38delta isoforms and the inhibition of proteasome activity are respectively responsible for the peroxynitrite-induced tau hyperphosphorylation and accumulation. PubMed:16816118

In the present study we injected bilaterally 3-morpholino-sydnonimine (SIN-1), a recognized and widely used peroxynitrite donor (25–30), into rat hippocampus, and investigated whether or not peroxynitrite could induce simultaneously nitration and hyperphosphorylation of tau and the underlying mechanisms in vivo. The level of nitrated and hyperphosphorylated tau was markedly increased in rat hippocampus 24 h, and prevented by preinjection of uric acid, a natural scavenger of peroxynitrite. GSK-3beta and p38 MAPKs, including p38alpha, p38beta, and p38delta activity was increased, but no change in the activity of p38gamma, ERK, and c-Jun amino-terminal kinase (JNK). Both nitrated tau and hyperphosphorylated tau were aggregated in the hippocampus, with activity of 20S proteasome significantly arrested in SIN-1-injected rats. Hyperphosphorylated tau was degraded as efficiently as normal tau by 20S proteasome, but the nitrated tau with an unorderly secondary structure became more resistant to the proteolysis, providing evidence that peroxynitrite simultaneously induces tau hyperphosphorylation, nitration, and accumulation, and that activation of GSK-3beta, p38alpha, p38beta, p38delta isoforms and the inhibition of proteasome activity are respectively responsible for the peroxynitrite-induced tau hyperphosphorylation and accumulation. PubMed:16816118

In the present study we injected bilaterally 3-morpholino-sydnonimine (SIN-1), a recognized and widely used peroxynitrite donor (25–30), into rat hippocampus, and investigated whether or not peroxynitrite could induce simultaneously nitration and hyperphosphorylation of tau and the underlying mechanisms in vivo. The level of nitrated and hyperphosphorylated tau was markedly increased in rat hippocampus 24 h, and prevented by preinjection of uric acid, a natural scavenger of peroxynitrite. GSK-3beta and p38 MAPKs, including p38alpha, p38beta, and p38delta activity was increased, but no change in the activity of p38gamma, ERK, and c-Jun amino-terminal kinase (JNK). Both nitrated tau and hyperphosphorylated tau were aggregated in the hippocampus, with activity of 20S proteasome significantly arrested in SIN-1-injected rats. Hyperphosphorylated tau was degraded as efficiently as normal tau by 20S proteasome, but the nitrated tau with an unorderly secondary structure became more resistant to the proteolysis, providing evidence that peroxynitrite simultaneously induces tau hyperphosphorylation, nitration, and accumulation, and that activation of GSK-3beta, p38alpha, p38beta, p38delta isoforms and the inhibition of proteasome activity are respectively responsible for the peroxynitrite-induced tau hyperphosphorylation and accumulation. PubMed:16816118

In the present study we injected bilaterally 3-morpholino-sydnonimine (SIN-1), a recognized and widely used peroxynitrite donor (25–30), into rat hippocampus, and investigated whether or not peroxynitrite could induce simultaneously nitration and hyperphosphorylation of tau and the underlying mechanisms in vivo. The level of nitrated and hyperphosphorylated tau was markedly increased in rat hippocampus 24 h, and prevented by preinjection of uric acid, a natural scavenger of peroxynitrite. GSK-3beta and p38 MAPKs, including p38alpha, p38beta, and p38delta activity was increased, but no change in the activity of p38gamma, ERK, and c-Jun amino-terminal kinase (JNK). Both nitrated tau and hyperphosphorylated tau were aggregated in the hippocampus, with activity of 20S proteasome significantly arrested in SIN-1-injected rats. Hyperphosphorylated tau was degraded as efficiently as normal tau by 20S proteasome, but the nitrated tau with an unorderly secondary structure became more resistant to the proteolysis, providing evidence that peroxynitrite simultaneously induces tau hyperphosphorylation, nitration, and accumulation, and that activation of GSK-3beta, p38alpha, p38beta, p38delta isoforms and the inhibition of proteasome activity are respectively responsible for the peroxynitrite-induced tau hyperphosphorylation and accumulation. PubMed:16816118

As regards the proteasome, both the ATP-dependent 26S proteasome and the ATP-independent 20S proteasome have been reported to degrade normal, soluble tau (Cardozo et al. 2002; Zhang et al. 2005). PubMed:22908190

As described above, it has also been found that the 20S proteasome interacts with tau aggregates (Keck et al. 2003). PubMed:22908190