Genetic Screens Yield Potential Therapies for Neurodegenerative Diseases
In Search of More Targets
The investigators next looked for genes that influence tau. Successive levels of genetic screening identified 59 genes that “robustly lower tau levels,” said Dr. Zoghbi. She and her colleagues prioritized 12 of the genes for investigation.
They used adenoassociated viral vectors to deliver therapies that can knock out mouse genes for as long as a year. With this technique, the investigators confirmed that all of the initial 12 genes decreased tau levels. In principle, this strategy could enable researchers to scan the whole genome for genes that modulate tau, said Dr. Zoghbi.
—Erik Greb
Suggested Reading
Lasagna-Reeves CA, de Haro M, Hao S, et al. Reduction of Nuak1 decreases tau and reverses phenotypes in a tauopathy mouse model. Neuron. 2016; 92(2):407-418.
Park J, Al-Ramahi I, Tan Q, et al. RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1. Nature. 2013;498(7454):325-331.
Rousseaux MW, de Haro M, Lasagna-Reeves CA, et al. TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau. Elife. 2016 Oct 25;5. pii: e19809
