Methamphetamine hijacks chaperone-mediated autophagy to degrade GPX4, driving ferroptosis-precipitated cognitive decline and addictive pathogenesis
Zizhen Si, Dan Zhu, Jianan Lv, Yang Shen, Xidi Wang, Jiahui Zhou, Zhiting Zou, Wenting Wei, Longhui Li, Xing Xu, Yaping Chen, Wenhua Zhou, Yu Liu · 2026
Read Methamphetamine hijacks chaperone-mediated autophagy to degrade GPX4, driving ferroptosis-precipitated cognitive decline and addictive pathogenesis by Zizhen Si, Dan Zhu, Jianan Lv, Yang Shen, Xidi Wang, Jiahui Zhou, Zhiting Zou, Wenting Wei, Longhui Li, Xing Xu, Yaping Chen, Wenhua Zhou, Yu Liu (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/PMC13501791.txt.
Description
Zizhen Si leads a thirteen-author team with a 2026 study of how methamphetamine damages the brain and entrenches addiction. Using rats that self-administer the drug, hippocampal neurons, and pathway-specific tools, the team followed a quality-control system called chaperone-mediated autophagy, which feeds chosen proteins to lysosomes for disposal. Methamphetamine coerced this machinery into grabbing GPX4, the enzyme that neutralizes oxidized fats, by exposing an unusual recognition tag on the protein.
Losing GPX4 broke glutathione recycling and unleashed ferroptosis, an iron-dependent cell death driven by fat peroxidation, across the hippocampus. Switching off the autophagy pathway in neurons rescued spatial memory and cut compulsive drug seeking, proving the pathway drives the harm rather than merely accompanying it. Blocking drugs aimed at this system eased the damage in early tests. The authors recast addiction's brain injury as hijacked protein housekeeping.
Catalog record
| CREATOR | Zizhen Si, Dan Zhu, Jianan Lv, Yang Shen, Xidi Wang, Jiahui Zhou, Zhiting Zou, Wenting Wei, Longhui Li, Xing Xu, Yaping Chen, Wenhua Zhou, Yu Liu |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 64778 |
| LICENSE | https://creativecommons.org/licenses/by/4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |