p(HGNC:TFEB)
TFEB at normal state is phosphorylated by mTOR complex 1, which inhibits its activity PubMed:29758300
mTORC1 also restrains autophagy by preventing nuclear translo- cation of TFEB 20 . PubMed:30116051
Moreover, the flavonol fisetin stimulated auto- phagic degradation of phosphorylated tau in cortical neu- rons via mTORC1-dependent activation of TFEB and the cytoprotective transcription factor nuclear factor eryth- roid 2-related factor 2 (NFE2L2) 149 . Fisetin also reduced Aβ accumulation in an APP/PS1 mouse model of AD 150 . PubMed:30116051
On the protein level, TFEB lysosomal target genes LAMP1 and Cathep- sin D (CTSD) are also increased in the FTD frontal cortex relative to normal subjects, and TFEB protein levels trended increased with statistical significance in the CBD group PubMed:30108137
Under starvation or stress, TFEB translocates to the nucleus and binds the CRE element to promote expression of macroautophagy and lysosomal genes [88]. PubMed:29758300
Another modulator of A-LS implicated in AD pathology is transcription factor EB (TFEB), a master regulator of lysosome biogenesis PubMed:29758300
Under starvation or stress, TFEB translocates to the nucleus and binds the CRE element to promote expression of macroautophagy and lysosomal genes [88]. PubMed:29758300
Another modulator of A-LS implicated in AD pathology is transcription factor EB (TFEB), a master regulator of lysosome biogenesis PubMed:29758300
Accordingly, overexpression of transcription factor EB (TFEB) was shown to correct lysosomal defects induced by the viral overexpression of a-syn and to downregulate the accumulation of oligomers in vivo [32]. PubMed:28803412
Unc-51-like kinase 1 (ULK1) is primarily an autophagy-initiating protein 3,10,19 , as is the mTORC1- suppressed transcrip- tion factor EB (TFEB), which orchestrates the synthesis of lysosomal and other proteins critical for maintaining ALN flux 20–23 . PubMed:30116051
mTORC1 also restrains autophagy by preventing nuclear translo- cation of TFEB 20 . PubMed:30116051
Indeed, TFEB over- expression reduced amyloid plaques in a APP/PS1 mouse model 148 . PubMed:30116051
TFEB activation has been linked to lysosomal stress and the ac- cumulation of aberrant protein aggregates, indicated by TFEB’s nuclear localization in lysosomal storage disorders PubMed:30108137
Transcriptional factor EB downregulates Aβ levels by affecting autophagy-lysosome (Zhang and Zhao 2015) PubMed:29626319
Xiao et al. have also obtained the consistent conclusion that transcriptional factor EB, a master regulator of lysosome biogenesis, improves lysosomal function in astrocytes, which may promote Aβ clearance and attenuate plaque pathogenesis (Xiao et al. 2014) PubMed:29626319
For example, like Aβ, clearance of pTau/NFT also can be regulated by TFEB, which increases the activity of autophagy and lysosome (Polito et al. 2014) PubMed:29626319
Xiao et al. have also obtained the consistent conclusion that transcriptional factor EB, a master regulator of lysosome biogenesis, improves lysosomal function in astrocytes, which may promote Aβ clearance and attenuate plaque pathogenesis (Xiao et al. 2014) PubMed:29626319
For example, like Aβ, clearance of pTau/NFT also can be regulated by TFEB, which increases the activity of autophagy and lysosome (Polito et al. 2014) PubMed:29626319
Xiao et al. have also obtained the consistent conclusion that transcriptional factor EB, a master regulator of lysosome biogenesis, improves lysosomal function in astrocytes, which may promote Aβ clearance and attenuate plaque pathogenesis (Xiao et al. 2014) PubMed:29626319
For example, like Aβ, clearance of pTau/NFT also can be regulated by TFEB, which increases the activity of autophagy and lysosome (Polito et al. 2014) PubMed:29626319
For example, like Aβ, clearance of pTau/NFT also can be regulated by TFEB, which increases the activity of autophagy and lysosome (Polito et al. 2014) PubMed:29626319
For example, like Aβ, clearance of pTau/NFT also can be regulated by TFEB, which increases the activity of autophagy and lysosome (Polito et al. 2014) PubMed:29626319
Another modulator of A-LS implicated in AD pathology is transcription factor EB (TFEB), a master regulator of lysosome biogenesis PubMed:29758300
TFEB has been shown to effectively clear phosphorylated tau proteins through A-LS, resulting in ameliorated neuronal loss and neuroinflammation, as well as improved cognitive performance [89]. PubMed:29758300
Another modulator of A-LS implicated in AD pathology is transcription factor EB (TFEB), a master regulator of lysosome biogenesis PubMed:29758300
TFEB has been shown to effectively clear phosphorylated tau proteins through A-LS, resulting in ameliorated neuronal loss and neuroinflammation, as well as improved cognitive performance [89]. PubMed:29758300
Activation of PTEN, another inducer of macroautophagy, by TFEB is indispensable for this TFEB-mediated increase in macroautophagy [89] PubMed:29758300
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