Chemical sensors detect and resolve proteome aggregation in peripheral neuropathy cell model induced by chemotherapeutic agents

Bioorg Chem. 2024 Jul:148:107491. doi: 10.1016/j.bioorg.2024.107491. Epub 2024 May 22.

Abstract

As a consequence of somatosensory nervous system injury or disease, neuropathic pain is commonly associated with chemotherapies, known as chemotherapy-induced peripheral neuropathy (CIPN). However, the mechanisms underlying CIPN-induced proteome aggregation in neuronal cells remain elusive due to limited detection tools. Herein, we present series sensors for fluorescence imaging (AggStain) and proteomics analysis (AggLink) to visualize and capture aggregated proteome in CIPN neuronal cell model. The environment-sensitive AggStain imaging sensor selectively binds and detects protein aggregation with 12.3 fold fluorescence enhancement. Further, the covalent AggLink proteomic sensor captures cellular aggregated proteins and profiles their composition via LC-MS/MS analysis. This integrative sensor platform reveals the presence of proteome aggregation in CIPN cell model and highlights its potential for broader applications in assessing proteome stability under various cellular stress conditions.

Keywords: Fluorescent imaging; Fluorescent sensor; Peripheral neuropathy; Protein aggregation; Proteomics.

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Dose-Response Relationship, Drug
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacology
  • Humans
  • Molecular Structure
  • Optical Imaging
  • Peripheral Nervous System Diseases* / chemically induced
  • Peripheral Nervous System Diseases* / metabolism
  • Protein Aggregates / drug effects
  • Proteome* / analysis
  • Proteome* / metabolism
  • Proteomics

Substances

  • Proteome
  • Antineoplastic Agents
  • Protein Aggregates
  • Fluorescent Dyes