Table 1.

TFEB relevant studies in Alzheimer’s disease.

TFEB Signaling mechanism	Tissue	Phenotype	Reference
Reduced TFEB expression resulted in lysosomal deficits	AD patient lymphocytes and monocytes		[79]
Selective nuclear TFEB exclusion	AD patient brain samples	Negative correlation between pathology & nuclear TFEB levels	[129]
TFEB is retained in cytosol hence lysosomal activity is reduced in AD patient fibroblasts & iPSC-derived human	Double presenilin KO cells, AD patient fibroblasts & iPSC-derived human AD neurons		[80]
APOE ɛ4 may compete with TFEB for binding to CLEAR elements in the lysosomal gene promoters & inhibition of the CLEAR network genes	APOE ɛ4/ɛ4 AD patients.		[130]
Increased TFEB expression	AD patient fibroblasts carrying the familial presenilin-1 A246E mutation		[131]
TFEB levels are unchanged however, upregulation of a subset of CLEAR network genes	presenilin-1 conditional KO mice		[132]
Transcriptome upregulation of TFEB targets	5x-FAD mice		[133]
Enhanced levels of TFEB and TFE3 resulted in elevated expression of autophagy target genes	Hippocampus of AD subjects		[77]
GSK inhibitor VIII induces TFEB nuclear translocation	reduced APP levels in vitro		[134]
CNS delivery of TFEB selectively cleared p-Tau species	rTg4510 mouse tauopathy model	Rescue of behavioral phenotypes, synaptic deficits, & neurodegeneration	[18]
Neuron specific TFEB overexpression resulted in decline of toxic p-Tau & lipofuscin levels in the cortex and hippocampus	P301S tauopathy mouse model	Improved performance in memory & learning tests	[81]
Astrocyte-specific delivery of TFEB promoted Aβ uptake & clearance	hippocampus of of APP/PS1 transgenic mice	Reduced Aβ levels & hippocampal plaque load	[19]
SIRT1 causes the deacetylation of TFEB increased lysosomal biogenesis & microglial degradation of fibrillary Aβ	ex vivo brain slices of APP/PS1 mice	Reduction of amyloid plaque	[135]
GCN5 causes TFEB acetylation leading to inhibition of autophagy and lysosome biogenesis	hTau Drosophila model	hTau aggregates & neurotoxicity	[136]
Curcumin analog C1 activated TFEB, increased autophagy and lysosomal activity	5xFAD, P301S and 3xTg-AD mice	Improved synaptic & cognitive function	[137]