An in vitro perspective on the molecular mechanisms underlying mutant huntingtin protein toxicity

被引:68
作者
Cisbani, G. [1 ]
Cicchetti, F. [1 ,2 ]
机构
[1] Ctr Rech CHUQ CHUL, Quebec City, PQ G1V 4G2, Canada
[2] Univ Laval, Dept Psychiat & Neurosci, Quebec City, PQ G1K 7P4, Canada
来源
CELL DEATH & DISEASE | 2012年 / 3卷
关键词
mutant huntingtin; aggregates; in vitro models; inflammation; inducible pluripotent stem cells; INCLUSION-BODY FORMATION; POLYGLUTAMINE-EXPANDED HUNTINGTIN; WILD-TYPE HUNTINGTIN; NEURONAL INTRANUCLEAR INCLUSIONS; DEPENDENT AGGREGATE FORMATION; PLURIPOTENT STEM-CELLS; PERIPHERAL-BLOOD CELLS; ALPHA-SYNUCLEIN; MOUSE MODEL; DISEASE PATIENTS;
D O I
10.1038/cddis.2012.121
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Huntington's disease (HD) is a devastating neurodegenerative disorder whose main hallmark is brain atrophy. However, several peripheral organs are considerably affected and their symptoms may, in fact, manifest before those resulting from brain pathology. HD is of genetic origin and caused by a mutation in the huntingtin gene. The mutated protein has detrimental effects on cell survival, but whether the mutation leads to a gain of toxic function or a loss of function of the altered protein is still highly controversial. Most currently used in vitro models have been designed, to a large extent, to investigate the effects of the aggregation process in neuronal-like cells. However, as the pathology involves several other organs, new in vitro models are critically needed to take into account the deleterious effects of mutant huntingtin in peripheral tissues, and thus to identify new targets that could lead to more effective clinical interventions in the early course of the disease. This review aims to present current in vitro models of HD pathology and to discuss the knowledge that has been gained from these studies as well as the new in vitro tools that have been developed, which should reflect the more global view that we now have of the disease. Cell Death and Disease (2012) 3, e382; doi: 10.1038/cddis.2012.121; published online 30 August 2012
引用
收藏
页码:e382 / e382
页数:12
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