In situ labeling of pathogenic Tau using photo-affinity chemical probes Research Letter
| Authors: | Nie, P.; Wu, Y.; Robinson, J.; Mekala, S.; Lee, V. M. Y.; Li, Y. M. |
| Title: | In situ labeling of pathogenic Tau using photo-affinity chemical probes |
| Abstract: | Tau aggregation plays a crucial role in the development of Alzheimer's disease (AD). Developing specific techniques that can isolate pathogenic tau from brain tissue is important for understanding tauopathies and advancing targeted therapies. Here, we develop photoaffinity small molecular probes and a novel method for in situ tissue labeling and investigate their activity in interacting with tau in cells and AD patient brains. Based on the reported chemical structures of tau PET tracers, we designed and synthesized two tau-specific probes, namely, Tau-2 and Tau-4. After validation in cell, mouse model, and patient brain samples, our photolabeling results suggested that Tau-2 effectively labels soluble tau in cell and mouse models, while Tau-4 selectively binds high-molecular-weight tau aggregates in late-stage AD patient brain tissues. Proteomic analysis verified the specific isolation of pathogenic tau from AD brain samples. Collectively, these findings underscore the potential of our photoaffinity probes as powerful tools for investigating tau proteins and neurofibrillary tangles in neurodegenerative diseases. |
| Keywords: | tracer; pet; positron-emission-tomography; inhibitors; cell; alzheimers-disease; insights; gamma-secretase; neurofibrillary tangles |
| Journal Title: | ACS Chemical Biology |
| Volume: | 20 |
| Issue: | 3 |
| ISSN: | 1554-8929 |
| Publisher: | American Chemical Society |
| Date Published: | 2025-03-21 |
| Start Page: | 581 |
| End Page: | 591 |
| Language: | English |
| ACCESSION: | WOS:001444305200001 |
| DOI: | 10.1021/acschembio.5c00073 |
| PROVIDER: | wos |
| PUBMED: | 40079621 |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding authors are You Wu and Yue-Ming Li -- Emily Yu's first name is listed as 'You' on the original publication -- Source: Wos |
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