Related Experiment Video
Updated: Jan 10, 2026
10:58
Focused Ion Beam Fabrication of LiPON-based Solid-state Lithium-ion Nanobatteries for In Situ Testing
Published on: March 7, 2018
10.6K
A Novel Lithium Ion-Assisted TPP Approach for Enhanced Target Discovery
Jingwen Yan1,2, Yiying Wu1,2, Yuyu Zhang1,2
1Institute of Integrative Medicine, Hebei Medical University, Shijiazhuang, 050017, China.
Analytical Chemistry
|November 28, 2025
Summary
Lithium ion-assisted thermal proteome profiling (Li-TPP) enhances detection of difficult-to-find proteins, including drug targets. This new method offers deeper insights into lithium
Area of Science:
- Proteomics
- Chemical Biology
- Neuroscience
Background:
- Traditional thermal proteome profiling (TPP) has limitations in detecting membrane and weakly bound proteins, potentially missing significant drug targets.
- Up to 20% of potential drug targets may be overlooked by conventional TPP methods.
- Improved methods are needed to comprehensively profile the proteome and understand drug mechanisms.
Purpose of the Study:
- To develop and validate a novel lithium ion-assisted thermal proteome profiling (Li-TPP) method.
- To enhance the detection of protein thermal stability, particularly for challenging protein classes.
- To gain mechanistic insights into lithium's therapeutic action in bipolar disorder.
Main Methods:
- Development of lithium ion-assisted thermal proteome profiling (Li-TPP).
- Application of Li-TPP to identify thermal shifts in proteins, including weakly bound and membrane proteins.
- Comparative analysis of Li-TPP against traditional TPP for protein identification and thermal displacement values.
- Functional enrichment analysis of Li-TPP identified proteins.
Main Results:
- Li-TPP significantly enhanced the detection of protein thermal stability compared to traditional TPP.
- Li-TPP identified 718 additional proteins and increased thermal displacement values in 368 co-identified proteins.
- The method successfully detected thermal shifts in weakly bound proteins (e.g., LDHA) and NMDA receptor complexes.
- Li-TPP identified known bipolar disorder targets (e.g., GSK3β) and novel regulatory proteins (e.g., CRMP2).
- Enrichment analysis revealed Li-TPP proteins involved in critical bipolar disorder pathways: microtubule dynamics, synaptic plasticity, and energy metabolism.
Conclusions:
- Li-TPP is a superior method for detecting challenging protein targets, including those missed by traditional TPP.
- The findings provide mechanistic insights into lithium's therapeutic effects, suggesting stabilization of neuronal energy homeostasis and microtubule architecture.
- Li-TPP offers a powerful platform for drug mechanism elucidation and the development of multitarget therapeutics for bipolar disorder.
