a(HBP:Neurodegeneration)

Entity

Name

Neurodegeneration

Namespace

HBP

Namespace Version

20181119

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/90e1cb9e5e882703380c9db8d4915ac6f3cba137/export/hbp-names.belns

TAU Interactions Section of NESTOR

Tau Modifications Sections of NESTOR

These results are consistent with previous in vitro studies and indicate that tau induces actin-filament bundling in vitro and F-actin accumulation in vivo, most likely through a direct interaction with F-actin.For genetic analysis, we selected a line of tauV337M-expressing flies that has a moderate rough eye and is a good substrate for genetic modification. Coexpressing an actin transgene (UAS–Act5C–EGFP;GMR– GAL4 driver) markedly enhanced tauV337M-induced toxicity. PubMed:17187063

These results are consistent with previous in vitro studies and indicate that tau induces actin-filament bundling in vitro and F-actin accumulation in vivo, most likely through a direct interaction with F-actin.For genetic analysis, we selected a line of tauV337M-expressing flies that has a moderate rough eye and is a good substrate for genetic modification. Coexpressing an actin transgene (UAS–Act5C–EGFP;GMR– GAL4 driver) markedly enhanced tauV337M-induced toxicity. PubMed:17187063

Triosephosphate isomerase (TPI) is a key enzyme in cell metabolism that controls the glycolytic flow and energy production through the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (G3P) (Richard, 1993). Notably, TPI is the only glycolytic enzyme whose functional deficiency is associated to neurodegeneration (Eber et al., 1991; Ovadi et al., 2004). In particular, inefficient glycolysis (Hoyer et al., 1988) and ATP depletion (Keil et al., 2004) are characteristic in Alzheimer’s disease brains. PubMed:19251756

hTau-K280Q mutants showed significantly increased phosphorylation on S262 as compared to both hTau-wt and hTau-K280R flies, when normalised to total hTau (K9JA) levels (**p < 0.01, one-way ANOVA, Fig. 4b,c). Mis-expression of pseudo-acetylated K280Q-hTau in the adult fly nervous system potently exacerbated fly locomotion defects and photoreceptor neurodegeneration. PubMed:26940749

The acetyl-mimicking mutant K174Q slows tau turnover and induces cognitive deficits in vivo. Acetyltransferase p300-induced tau acetylation is inhibited by salsalate and salicylate, which enhance tau turnover and reduce tau levels. In the PS19 transgenic mouse model of FTD, administration of salsalate after disease onset inhibited p300 activity, lowered levels of total tau and tau acetylated at K174, rescued tau-induced memory deficits and prevented hippocampal atrophy. PubMed:26390242

Using transgenic Drosophila expressing human tau, we found that RNAi-mediated knockdown of milton or Miro, an adaptor protein essential for axonal transport of mitochondria, enhanced human tau-induced neurodegeneration. Tau phosphorylation at an AD-related site Ser262 increased with knockdown of milton or Miro; and partitioning defective-1 (PAR-1), the Drosophila homolog of mammalian microtubule affinity-regulating kinase, mediated this increase of tau phosphorylation. Tau phosphorylation at Ser262 has been reported to promote tau detachment from microtubules, and we found that the levels of microtubule-unbound free tau increased by milton knockdown. Blocking tau phosphorylation at Ser262 site by PAR-1 knockdown or by mutating the Ser262 site to unphosphorylatable alanine suppressed the enhancement of tau-induced neurodegeneration caused by milton knockdown. Furthermore, knockdown of milton or Miro increased the levels of active PAR-1. PubMed:22952452

These results are consistent with previous in vitro studies and indicate that tau induces actin-filament bundling in vitro and F-actin accumulation in vivo, most likely through a direct interaction with F-actin.For genetic analysis, we selected a line of tauV337M-expressing flies that has a moderate rough eye and is a good substrate for genetic modification. Coexpressing an actin transgene (UAS–Act5C–EGFP;GMR– GAL4 driver) markedly enhanced tauV337M-induced toxicity. PubMed:17187063

Triosephosphate isomerase (TPI) is a key enzyme in cell metabolism that controls the glycolytic flow and energy production through the interconversion of dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (G3P) (Richard, 1993). Notably, TPI is the only glycolytic enzyme whose functional deficiency is associated to neurodegeneration (Eber et al., 1991; Ovadi et al., 2004). In particular, inefficient glycolysis (Hoyer et al., 1988) and ATP depletion (Keil et al., 2004) are characteristic in Alzheimer’s disease brains. PubMed:19251756

Using transgenic Drosophila expressing human tau, we found that RNAi-mediated knockdown of milton or Miro, an adaptor protein essential for axonal transport of mitochondria, enhanced human tau-induced neurodegeneration. Tau phosphorylation at an AD-related site Ser262 increased with knockdown of milton or Miro; and partitioning defective-1 (PAR-1), the Drosophila homolog of mammalian microtubule affinity-regulating kinase, mediated this increase of tau phosphorylation. Tau phosphorylation at Ser262 has been reported to promote tau detachment from microtubules, and we found that the levels of microtubule-unbound free tau increased by milton knockdown. Blocking tau phosphorylation at Ser262 site by PAR-1 knockdown or by mutating the Ser262 site to unphosphorylatable alanine suppressed the enhancement of tau-induced neurodegeneration caused by milton knockdown. Furthermore, knockdown of milton or Miro increased the levels of active PAR-1. PubMed:22952452