Time: 16:00-17:30 on Tue.,Oct.24, 2023
Speaker: Dr.Fen-Biao Gao
Host: Dr.Song-Hai Shi
Title: Pathogenic Mechanisms and Therapeutic Targets in Frontotemporal Dementia and ALS
Frontotemporal dementia (FTD) is the most common pre-senile dementia before age of 60 that shares extensive genetic and pathological overlaps with the motor neuron disease amyotrophic lateral sclerosis (ALS). In recent years, many disease-causing mutations have been identified in genes such as CHMP2B, GRN, TDP-43, C9ORF72 and others. Among them, GGGGCC (G4C2) repeat expansion in the first intron of C9ORF72 is the most common genetic cause of both FTD and ALS. Both sense and antisense repeat RNAs can be translated into different dipeptide repeat (DPR) proteins. In this talk, I will discuss how poly (GR) disrupts multiple molecular pathways in fruitfly Drosophila and patient iPSC-derived neurons and how these insights can be used to develop therapeutic approaches.
(Recent representative publications: Freibaum*, Lu* et al., Nature 2015; Tran et al., Neuron 2015; Lopez-Gonzalez et al., Neuron 2016; Lopez-Gonzalez et al., PNAS 2019; Choi et al., Nat. Neurosci. 2019; Yuva-Aydemir et al., Nat. Commun. 2019; Loveland et al., Nat. Commun. 2022; Lee et al., Neuron 2023).