Doxycycline Interferes With Tau Aggregation and Reduces Its Neuronal Toxicity

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Tauopathies are a class of neurodegenerative diseases with rising incidence and no current cure.
• Developing new treatments is time-consuming, necessitating the exploration of repurposing existing safe drugs.
• Doxycycline has previously shown effects on alpha-synuclein aggregation.

Purpose of the Study:

• To investigate the effect of doxycycline on tau protein aggregation and toxicity.
• To evaluate doxycycline's potential as a therapeutic agent for tauopathies.

Main Methods:

• In vitro experiments assessing doxycycline's impact on tau protein aggregation (2N4R and K18 isoforms).
• Cell-free assays to examine tau seeding inhibition by doxycycline.
• Cell culture models to determine doxycycline's effect on tau aggregate toxicity.

Main Results:

• Doxycycline demonstrated a dose-dependent reduction in the amyloid aggregation of tau protein isoforms.
• The drug was found to prevent tau seeding in cell-free systems.
• Doxycycline treatment decreased the toxicity of tau aggregates in cell cultures.

Conclusions:

• Doxycycline exhibits efficacy against tau aggregation and toxicity, expanding its known therapeutic actions.
• Repurposing doxycycline presents a promising avenue for developing disease-modifying therapies for tauopathies.