Related Experiment Video
Updated: Jun 21, 2025
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
Macrocyclic peptides derived from AcPHF6* and AcPHF6 to selectively modulate the Tau aggregation
Abha Dangi1, Tazeen Qureshi2, Subashchandrabose Chinnathambi2
1Central NMR Facility, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, 411008 Pune, India; Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, 411008 Pune, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-HRDC Campus, Sector 19, Kamla Nehru Nagar, Ghaziabad, UP, 201002, India.
Researchers designed novel peptides to control Tau aggregation. Two peptides, P3 and P8, were identified to either promote or inhibit Tau aggregation, offering potential therapeutic applications.
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroscience
Background:
- Tau aggregation is central to neurodegenerative diseases like Alzheimer's.
- Understanding and controlling Tau aggregation is crucial for therapeutic development.
Purpose of the Study:
- To design and synthesize novel macrocyclic peptides to modulate Tau aggregation.
- To identify peptides that selectively promote or inhibit Tau aggregation.
Main Methods:
- Peptide design based on Tau aggregation models (AcPHF6* and AcPHF6).
- Synthesis of ten 14-amino acid macrocyclic peptides.
- NMR analysis for structural conformation.
- Self-aggregation and cross-aggregation studies.
- Assessment of effects on K18wt aggregation.
Main Results:
- All synthesized peptides adopted an antiparallel β-sheet conformation.
- Peptide P3 showed high aggregation tendency, while P8 showed low aggregation tendency.
- P3 promoted aggregation of parent peptides and K18wt, while P8 reduced it.
- P3 and P8 demonstrated selective pro- and anti-aggregation effects on Tau.
Conclusions:
- Structurally defined peptides (P3 and P8) can modulate Tau aggregation.
- These peptides offer potential applications in Tau model studies.
- Development of Tau aggregation inhibitors or promoters is facilitated by these findings.
