# Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies

## TL;DR

This review explores combining therapies targeting two protein-clearance systems to treat diseases caused by protein buildup in the brain.

## Contribution

The paper proposes dual targeting of the UPS and autophagy as a novel therapeutic strategy for neurodegenerative diseases.

## Key findings

- The UPS and autophagy pathways interact and share regulatory components.
- Modulating both systems together may improve protein clearance in neurodegenerative diseases.
- Emerging evidence supports the potential of combined therapies for treating proteinopathies.

## Abstract

Neurodegenerative proteinopathies are characterized by impaired protein clearance and the accumulation of misfolded or aggregated proteins, ultimately leading to neuronal death. The two principal pathways responsible for protein degradation in cells are the ubiquitin proteasome system (UPS) and autophagy. Emerging evidence indicates that these pathways share regulatory components and engage in extensive crosstalk. In this review, we summarize the mechanisms of the UPS and autophagy, highlight their points of interaction, and discuss therapeutic opportunities to modulate both systems in parallel to enhance protein clearance in neurodegenerative disease.