p(HGNC:MAPT, var("?"))
Moreover, the M1 agonist AF267B can rescue the cognitive impairment and decrease Aβ42 and tau abnormalities in the cortex and hippocampus of a mouse model of AD PubMed:26813123
Truncation of Tau by caspases and endopeptidases has been suggested to constitute an important pathogenic step in AD PubMed:29215007
Truncation of Tau by caspases and endopeptidases has been suggested to constitute an important pathogenic step in AD PubMed:29215007
Truncation of Tau by caspases and endopeptidases has been suggested to constitute an important pathogenic step in AD PubMed:29215007
Together, multiple studies suggest that Hsp90 regulates the stability of both phospho- and mutant-tau PubMed:21882945
Previous studies have shown that Hsp90 inhibition decreased the levels of hyperphosphorylated and/or mutated tau species both in cells and mice. PubMed:29311797
After 15 min of heparin exposure, we detected low but significant amounts of seed-compe- tent monomer, and much fewer larger assemblies (Figure 6A). PubMed:29988016
Both aggregates and mutant forms of tau likewise block the proteasome, and its ability to degrade hyper- phosphorylated and oligomeric tau is reduced compared with its ability to degrade physiological tau 3,55,68 . PubMed:30116051
Finally, while physiological tau possesses KFERQ motifs and is degraded by CMA, aggregates, mutant forms and frag- ments interfere with CMA 45,47 . PubMed:30116051
Truncation of Tau by caspases and endopeptidases has been suggested to constitute an important pathogenic step in AD PubMed:29215007
However, under potentially proteotoxic conditions, the post-translational modifications or mutations that damage tau’s affinity for microtubules and favor its aggregation are thought to generate a molecular ‘danger signal’ that specifically alerts the quality control system [112,113]. PubMed:21882945
However, under potentially proteotoxic conditions, the post-translational modifications or mutations that damage tau’s affinity for microtubules and favor its aggregation are thought to generate a molecular ‘danger signal’ that specifically alerts the quality control system [112,113]. PubMed:21882945
Notably, tau missense mutations found in frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17; Goedert et al.,2000) and AD-mimicking tau phosphorylation in proline-rich motifs (Eidenmuller et al.,2001) inhibit the association of tau with PP2A (Figure3B). PubMed:24653673
In familial tauopathies, the mutation of MAPT seems to be the cause of tau aggregation, but in sporadic tauopathies (such as AD), the trigger of tau pathology is unclear. PubMed:26631930
However Ms induced amyloid forma- tion, albeit more slowly than trimer or unfractionated fibrils (Figure 1F). PubMed:29988016
Hyperphosphorylation, mutations and overexpression of tau can drive the mislocalization of tau into postsynaptic spines, resulting in synaptic dysfunction PubMed:26631930
Hyperphosphorylation, mutations and overexpression of tau can drive the mislocalization of tau into postsynaptic spines, resulting in synaptic dysfunction PubMed:26631930
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