Current insights into the C9orf72 repeat expansion diseases of the FTLD/ALS spectrum

被引：133

作者：

Cruts, Marc ^{[1
,2
]}

Gijselinck, Ilse ^{[1
,2
]}

Van Langenhove, Tim ^{[1
,2
]}

van der Zee, Julie ^{[1
,2
]}

Van Broeckhoven, Christine ^{[1
,2
]}

机构：

[1] VIB, Neurodegenerat Brain Dis Grp, Dept Mol Genet, B-2610 Antwerp, Belgium

[2] Univ Antwerp, Neurogenet Lab, Inst Born Bunge, B-2610 Antwerp, Belgium

来源：

TRENDS IN NEUROSCIENCES | 2013年 / 36卷 / 08期

关键词：

C9orf72; amyotrophic lateral sclerosis; frontotemporal lobar degeneration; TDP43-proteinopathy; repeat expansion diseases; neurodegeneration; AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION; GGGGCC HEXANUCLEOTIDE REPEAT; INCLUSION-BODY MYOPATHY; CLINICAL CHARACTERISTICS; SCLEROSIS/FRONTOTEMPORAL DEMENTIA; SQSTM1; MUTATIONS; GENE; ALS; TDP-43;

D O I：

10.1016/j.tins.2013.04.010

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

An expanded G(4)C(2) hexanucleotide repeat in the proximal regulatory region of C9orf72 is a frequent cause of neurodegenerative diseases in the frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND) spectrum. Although primarily characterized by variably abundant pathological inclusions of TDP-43 protein, the lesion load was extended to TDP-43-negative, p62-positive neuronal and glial inclusions in extended regions of the central nervous system (CNS), particularly in cerebellum, where they may be characteristic of a C9orf72 repeat expansion. Disease mechanisms associated with repeat expansion disorders, including haploinsufficiency, RNA toxicity, and abnormal translation of expanded repeat sequences, are beginning to emerge. We review genetic, clinical, and pathological highlights and discuss current insights into the biology of this novel type of repeat expansion disease.

引用

页码：450 / 459

页数：10

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