Mutant Tau (P301L) Enhances Global Protein Translation in Differentiated SH-SY5Y Cells by Upregulating mTOR...

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Altered protein synthesis is implicated in aging and neurodegenerative diseases like Alzheimer's.
• Hyperphosphorylated Tau accumulation in tauopathies disrupts cellular processes, including mRNA translation.
• The precise impact of Tau on global protein synthesis in human neurons is not fully understood.

Purpose of the Study:

• To investigate the effects of mutant Tau protein expression on global protein synthesis in human neurons.
• To elucidate the molecular pathways involved in Tau-mediated translational regulation.

Main Methods:

• Utilized SH-SY5Y cells overexpressing the P301L mutant Tau protein.
• Quantified global protein synthesis using the Surface Sensing of Translation (SUnSET) puromycin-incorporation assay.
• Assessed the role of the mTOR/S6 pathway and the effect of rapamycin treatment.

Main Results:

• Expression of Tau-P301L significantly increased global protein synthesis.
• This upregulation was mediated by the activation of the mTOR/S6 signaling pathway.
• Rapamycin treatment abolished the Tau-induced increase in translation, confirming mTOR dependency.

Conclusions:

• Mutant Tau protein enhances global protein synthesis in human neurons via mTOR/S6 pathway activation.
• Tau-induced translational alterations may contribute to the progression of tauopathies.
• The mTOR signaling pathway represents a potential therapeutic target for tauopathies.