title: Structural insight into C9orf72 hexanucleotide repeat expansions: Towards new therapeutic targets in FTD-ALS.
abstract: Hexanucleotide repeat expansions, (G4C2) in the C9orf72 gene are considered as the single most common genetic cause of both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). (G4C2), either as DNA or the transcribed RNA, can folds into unusual secondary structures, including G-quadruplex, R-loop, I-motif and hairpin. These structural polymorphism at both DNA and RNA levels were proposed to initiate molecular cascade leading to ALS/FTD. G-quadruplexes are composed of stacked G4 tetrads, held by hydrophobic bonds, and is highly stable secondary structure. Here, we covers the structural and functional features of G-quadruplexes with an emphasis on C9orf72-repeat-associated FTD and ALS (C9-FTD/ALS). We also highlighted tools and techniques used to study the G-quadruplexes. Current perspectives for molecules that target G-quadruplexes as potential therapeutic are discussed. Our extensive analysis of structural features of G-quadruplexes will be used for a better understanding of molecular mechanism of C9-FTD/ALS.
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Centre for Biological Sciences, Central University of South Bihar, Patna, 800014, India.
authors.forename: Tara
authors.initials: T
authors.lastname: Kashav
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
authors.forename: Asimul
authors.initials: A
authors.lastname: Islam
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
authors.forename: Faizan
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India. Electronic address: mihassan@jmi.ac.in.
authors.forename: Md Imtaiyaz
authors.initials: MI
authors.lastname: Hassan
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D004247:DNA / Q000235:genetics; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000628:therapy; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D008958:Models, Molecular; D012313:RNA / Q000235:genetics
chemical_list: D012313:RNA; D004247:DNA
keywords: Amyotrophic lateral sclerosis; C9-FTD/ALS; C9orf72; Frontotemporal dementia; G-quadruplexes; Therapy