Abstract：
:Amyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressing neurodegenerative disease affecting motor neurons, and frontotemporal dementia (FTD) is a behavioural disorder resulting in early-onset dementia. Hexanucleotide (G4C2) repeat expansions in the gene encoding chromosome 9 open reading frame 72 (C9orf72) are the major cause of familial forms of both ALS (~40%) and FTD (~20%) worldwide. The C9orf72 repeat expansion is known to form abnormal nuclei acid structures, such as hairpins, G-quadruplexes, and R-loops, which are increasingly associated with human diseases involving microsatellite repeats. These configurations form during normal cellular processes, but if they persist they also damage DNA, and hence are a serious threat to genome integrity. It is unclear how the repeat expansion in C9orf72 causes ALS, but recent evidence implicates DNA damage in neurodegeneration. This may arise from abnormal nucleic acid structures, the greatly expanded C9orf72 RNA, or by repeat-associated non-ATG (RAN) translation, which generates toxic dipeptide repeat proteins. In this review, we detail recent advances implicating DNA damage in C9orf72-ALS. Furthermore, we also discuss increasing evidence that targeting these aberrant C9orf72 confirmations may have therapeutic value for ALS, thus revealing new avenues for drug discovery for this disorder.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Konopka A,Atkin JDdoi
10.3390/ijms19103137subject
Has Abstractpub_date
2018-10-12 00:00:00issue
10issn
1422-0067pii
ijms19103137journal_volume
19pub_type
杂志文章,评审abstract：:Neuromuscular disorders (NMDs) affect 1 in 3000 people worldwide. There are more than 150 different types of NMDs, where the common feature is the loss of muscle strength. These disorders are classified according to their neuroanatomical location, as motor neuron diseases, peripheral nerve diseases, neuromuscular junc...
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更新日期：2020-05-08 00:00:00
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