Fig. 8: Proposed involvement of G4 in Neurodegenerative diseases.

As a key pathogenic gene of ALS/FTD, G4-forming in the promoter region of C9orf72 can inhibit its transcription. In particular, G4s also recruits hemin, leading to DNA oxidative damage. Formation of G4s in the promoter of Gad1 and Th inhibit their transcription and further affects the synthesis of GABA and Dopamine. G4 formed in the 5′UTR region of α -SnCA, ADAM mRNA, and the 3′UTR region of APP mRNA can directly inhibit translation. However, G4 formed in the BACE1 mRNA 3′UTR region can recruit heterogeneous nuclear ribonucleoprotein H (hnRNPH), promote its translation, and induce the formation of APP, which are involved in the pathogenesis of AD and PD.