# GV1001 reduces pathological 4R tau and functional deficits in models relevant to progressive supranuclear palsy

## TL;DR

GV1001, a drug derived from human telomerase, reduces harmful 4R tau protein and improves symptoms in models of progressive supranuclear palsy, a rare brain disorder.

## Contribution

GV1001 is shown for the first time to reduce 4R tau in models of progressive supranuclear palsy, suggesting new therapeutic potential.

## Key findings

- GV1001 reduced 4R tau protein levels in a PSP-related neuronal model.
- In a mouse model of PSP, GV1001 also reduced 4R tau protein levels.
- The drug shows potential as a disease-modifying treatment for 4R tauopathies like PSP.

## Abstract

GV1001, a peptide drug derived from human telomerase reverse transcriptase, has showed the therapeutic effect in the animal model of Alzheimer’s disease (AD), a representative chronic neurodegenerative disease having impaired learning and memory. In our previous studies, GV1001 has showed the multi-functions including anti-apoptosis, anti-oxidative stress, and anti-neuroinflammation in AD-related in vitro and in vivo systems. Here, in addition to these previously reported functions, GV1001 was discovered to reduce the protein level of 4R tau isoform in the pathological condition. There is no studies providing the potential of GV1001 as a therapeutic drug for neurodegenerative movement disorders. Progressive supranuclear palsy (PSP) is a rare atypical Parkinsonism in the midbrain region, leading to more severe motor symptoms and very rapid pathological progression. Increased 4R tau isoform in an affected brain region of the primary 4R tauopathy is a distinct pathological character in PSP patients. In this study, GV1001 down-regulated the protein level of 4R tau specifically in an annonacin-induced PSP in vitro neuronal model as well as in vivo study using 4R TauP301L-BiFC mouse model. These findings suggest a novel role of GV1001 in 4R tauopathy and support its disease-modifying potential within the context of 4R tau–driven neurodegenerative models, including PSP.

The online version contains supplementary material available at 10.1038/s41598-026-42195-7.