Balendra, R;
Isaacs, AM;
(2018)
C9orf72-mediated ALS and FTD: multiple pathways to disease.
Nature Reviews Neurology
, 14
(9)
pp. 544-558.
10.1038/s41582-018-0047-2.
Preview |
Text
Balendra & Isaacs Nat Rev Neurol final accepted version.pdf - Accepted Version Download (1MB) | Preview |
Abstract
The discovery that repeat expansions in the C9orf72 gene are a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) has revolutionized our understanding of these diseases. Substantial headway has been made in characterizing C9orf72-mediated disease and unravelling its underlying aetiopathogenesis. Three main disease mechanisms have been proposed: loss of function of the C9orf72 protein and toxic gain of function from C9orf72 repeat RNA or from dipeptide repeat proteins produced by repeat-associated non-ATG translation. Several downstream processes across a range of cellular functions have also been implicated. In this article, we review the pathological and mechanistic features of C9orf72-associated FTD and ALS (collectively termed C9FTD/ALS), the model systems used to study these conditions, and the probable initiators of downstream disease mechanisms. We suggest that a combination of upstream mechanisms involving both loss and gain of function and downstream cellular pathways involving both cell-autonomous and non-cell-autonomous effects contributes to disease progression.
Type: | Article |
---|---|
Title: | C9orf72-mediated ALS and FTD: multiple pathways to disease |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1038/s41582-018-0047-2 |
Publisher version: | http://dx.doi.org/10.1038/s41582-018-0047-2 |
Language: | English |
Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
Keywords: | Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences & Neurology, AMYOTROPHIC-LATERAL-SCLEROSIS, DIPEPTIDE-REPEAT PROTEINS, FRONTOTEMPORAL LOBAR DEGENERATION, C9ORF72 HEXANUCLEOTIDE REPEAT, STRESS GRANULE FORMATION, G-QUADRUPLEX STRUCTURES, RNA-BINDING PROTEINS, BAC TRANSGENIC MICE, MOUSE MODEL, NUCLEOCYTOPLASMIC TRANSPORT |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
URI: | https://discovery.ucl.ac.uk/id/eprint/10058232 |
Archive Staff Only
View Item |