Biomedicines (Jun 2024)

Synthesis and Characterization of Click Chemical Probes for Single-Cell Resolution Detection of Epichaperomes in Neurodegenerative Disorders

  • Sadik Bay,
  • Chander S. Digwal,
  • Ananda M. Rodilla Martín,
  • Sahil Sharma,
  • Aleksandra Stanisavljevic,
  • Anna Rodina,
  • Anoosha Attaran,
  • Tanaya Roychowdhury,
  • Kamya Parikh,
  • Eugene Toth,
  • Palak Panchal,
  • Eric Rosiek,
  • Chiranjeevi Pasala,
  • Ottavio Arancio,
  • Paul E. Fraser,
  • Melissa J. Alldred,
  • Marco A. M. Prado,
  • Stephen D. Ginsberg,
  • Gabriela Chiosis

DOI
https://doi.org/10.3390/biomedicines12061252
Journal volume & issue
Vol. 12, no. 6
p. 1252

Abstract

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Neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), represent debilitating conditions with complex, poorly understood pathologies. Epichaperomes, pathologic protein assemblies nucleated on key chaperones, have emerged as critical players in the molecular dysfunction underlying these disorders. In this study, we introduce the synthesis and characterization of clickable epichaperome probes, PU-TCO, positive control, and PU-NTCO, negative control. Through comprehensive in vitro assays and cell-based investigations, we establish the specificity of the PU-TCO probe for epichaperomes. Furthermore, we demonstrate the efficacy of PU-TCO in detecting epichaperomes in brain tissue with a cellular resolution, underscoring its potential as a valuable tool for dissecting single-cell responses in neurodegenerative diseases. This clickable probe is therefore poised to address a critical need in the field, offering unprecedented precision and versatility in studying epichaperomes and opening avenues for novel insights into their role in disease pathology.

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