Related Experiment Video
Updated: Nov 2, 2025
09:05
Pooled CRISPR-Based Genetic Screens in Mammalian Cells
Published on: September 4, 2019
22.5K
Genome-wide CRISPR screen identifies protein pathways modulating tau protein levels in neurons
Carlos G Sanchez1, Christopher M Acker1, Audrey Gray1
1Department of Neuroscience, Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
Communications Biology
|June 15, 2021
Summary
Researchers identified key genes controlling tau protein levels using a genome-wide CRISPR screen. This discovery offers new therapeutic targets for neurodegenerative diseases like Alzheimer's.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Hyperphosphorylated tau protein aggregates are hallmarks of over 20 neurodegenerative diseases.
- The precise mechanisms driving tau aggregation and its link to disease progression remain unclear.
Purpose of the Study:
- To identify genetic modulators of endogenous tau protein levels for the first time.
- To uncover novel pathways regulating tau accumulation relevant to neurodegenerative disease.
Main Methods:
- Genome-wide CRISPR screening in SH-SY5Y cells to find tau protein regulators.
- Validation of candidate genes using Ngn2-induced human cortical excitatory neurons.
- In vivo validation of key identified genes, such as TSC1.
Main Results:
- Identified both positive and negative regulators of endogenous tau protein levels.
- Discovered involvement of chromatin modifiers, neddylation/ubiquitin pathways, and mTOR pathway components.
- Validated TSC1, an mTOR pathway component, as a significant modulator of tau levels.
Conclusions:
- The study successfully identified novel genetic regulators of tau protein.
- These findings provide potential therapeutic targets for treating tauopathies and related neurodegenerative diseases.
