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Updated: Jul 13, 2025

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Aggregation, Transmission, and Toxicity of the Microtubule-Associated Protein Tau: A Complex Comprehension

Jiaxin Hu1, Wenchi Sha1, Shuangshuang Yuan1

  • 1Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.

International Journal of Molecular Sciences
|October 14, 2023
PubMed

Insights

Microtubule-associated protein tau aggregates in neurodegenerative diseases like Alzheimer's. This review covers tau protein aggregation, transmission, and toxicity, advancing understanding of tauopathies.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Cell Biology

Background:

  • Microtubule-associated protein tau (tau) is intrinsically disordered, interacting with microtubules (MTs).
  • Pathological tau modification leads to detachment from MTs and aggregation in neurodegenerative diseases (tauopathies).
  • Tauopathies include Alzheimer's disease (AD), frontotemporal dementia (FTD), and corticobasal degeneration (CBD).

Purpose of the Study:

  • To review current understanding of tau protein aggregation mechanisms.
  • To discuss the intercellular transmission of pathological tau species.
  • To explore the structural and conformational aspects of tau polymerization and aggregate toxicity.

Main Methods:

  • Literature review of recent advancements in tau protein research.
  • Synthesis of findings on tau structure, aggregation, and intercellular spread.
  • Discussion of ongoing debates regarding tau aggregate toxicity.

Main Results:

  • Significant progress has been made in understanding tau transmission and aggregate structures.
  • Conformational changes during tau polymerization are key to aggregate formation.
  • The precise mechanisms of tau aggregation and the toxicity of these aggregates remain areas of active investigation.

Conclusions:

  • Tau aggregation is central to tauopathies, but the exact process and toxicity are still debated.
  • Understanding tau transmission and aggregation is crucial for developing therapeutic strategies.
  • Further research into tau's conformational dynamics and intercellular spread is needed.
Keywords:
tau aggregatestau toxicitytau transmissiontauopathy

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