# Novel role of β-arrestins in Tauopathy

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2021 · $373,750

## Abstract

The major defining pathological hallmarks of Alzheimer’s disease (AD) are the accumulation of
amyloid β (Aβ) and hyperphosphorylated tau. Multiple GPCRs (i.e, β2AR, GPR3, AT2R, CXCR2,
& NMDARs) have been shown to play integral roles in AD pathogenesis. However, it is unclear
as to how a diverse array of GPCRs all positively impinge on Aβ and tau pathogenesis as well as
neurodegeneration in AD. Given that GPCRs share a common mechanism of action via β-arrestin
scaffolding signaling complexes, the central hypothesis is that the actions of β-arrestins
downstream of GPCRs directly impact AD pathogenesis. β-arrestins exist in three distinct states
in cells; 1) free unbound, 2) GPCR-bound, and 3) microtubule-bound, each with different signaling
capability. Previous studies have shown that β-arrestins are upregulated in AD brains and that β-
arrestins promote Aβ pathogenesis. However, it is unknown whether and how β-arrestins
pathogenically impinge on tauopathy and neurodegeneration in AD. Preliminary data indicate that
β-arrestin oligomers promote tauopathy via 2 distinct mechanisms: 1) directly competing with tau
for binding to microtubules (MT), thereby deregulating MT dynamics; 2) inhibiting tau clearance
by deregulating the autophagy machinery.
By utilizing molecular, cell biological, biochemical, electrophysiological, behavioral, viral, and
histochemical tools, this proposal will 1) validate the role of β-arrestins in tauopathy in vivo, 2)
validate the role of β-arrestins in tau/microtubule dynamics, and 3) investigate the role of β-
arrestins in p62-mediated autophagy and tau turnover. This proposal will validate whether β-
arrestins and their oligomeric status serve as promising therapeutic targets to mitigate tau
pathogenesis.

## Key facts

- **NIH application ID:** 10094176
- **Project number:** 5R01AG059721-03
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** JungA Alexa Woo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $373,750
- **Award type:** 5
- **Project period:** 2019-05-15 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10094176

## Citation

> US National Institutes of Health, RePORTER application 10094176, Novel role of β-arrestins in Tauopathy (5R01AG059721-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10094176. Licensed CC0.

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