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  • Optical induction of autophagy via Transcription factor EB (TFEB) reduces pathological tau in neurons.

Optical induction of autophagy via Transcription factor EB (TFEB) reduces pathological tau in neurons.

PloS one (2020-03-26)
Jessica L Binder, Praveen Chander, Vojo Deretic, Jason P Weick, Kiran Bhaskar
ABSTRACT

Pathological accumulation of microtubule associated protein tau in neurons is a major neuropathological hallmark of Alzheimer's disease (AD) and related tauopathies. Several attempts have been made to promote clearance of pathological tau (p-Tau) from neurons. Transcription factor EB (TFEB) has shown to clear p-Tau from neurons via autophagy. However, sustained TFEB activation and autophagy can create burden on cellular bioenergetics and can be deleterious. Here, we modified previously described two-plasmid systems of Light Activated Protein (LAP) from bacterial transcription factor-EL222 and Light Responsive Element (LRE) to encode TFEB. Upon blue-light (465 nm) illumination, the conformation changes in LAP induced LRE-driven expression of TFEB, its nuclear entry, TFEB-mediated expression of autophagy-lysosomal genes and clearance of p-Tau from neuronal cells and AD patient-derived human iPSC-neurons. Turning the blue-light off reversed the expression of TFEB-target genes and attenuated p-Tau clearance. Together, these results suggest that optically regulated TFEB expression unlocks the potential of opto-therapeutics to treat AD and other dementias.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Tau Antibody, clone Tau 12, clone Tau 12, from mouse
Sigma-Aldrich
Anti-GAPDH Mouse mAb (6C5), liquid, clone 6C5, Calbiochem®