Abstract
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two age-dependent multifactorial neurodegenerative disorders, which are typically characterized by the selective death of motor neurons and cerebral cortex neurons, respectively. These two diseases share many clinical, genetic and pathological aspects. During the past decade, cell reprogramming technologies enabled researchers to generate human induced pluripotent stem cells (iPSCs) from somatic cells. This resulted in the unique opportunity to obtain specific neuronal and non-neuronal cell types from patients which could be used for basic research. Moreover, these in vitro models can mimic not only the familial forms of ALS/FTD, but also sporadic cases without known genetic cause. At present, there have been extensive technical advances in the generation of iPSCs, as well as in the differentiation procedures to obtain iPSC-derived motor neurons, cortical neurons and non-neuronal cells. The major challenge at this moment is to determine whether these iPSC-derived cells show relevant phenotypes that recapitulate complex diseases. In this review, we will summarize the work related to iPSC models of ALS and FTD. In addition, we will discuss potential drawbacks and solutions for establishing more trustworthy iPSC models for both ALS and FTD.
Highlights
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the selective death of both upper and lower motor neurons (Renton et al, 2014)
The research group of Chandran first described a human motor neuron model derived from induced pluripotent stem cells (iPSCs) from an ALS patient carrying the TDP-43M337V mutation (Egawa et al, 2012)
In 2013, three groups generated iPSCs from ALS/frontotemporal dementia (FTD) patients carrying the chromosome 9 open reading frame 72 (C9ORF72) mutation (Almeida et al, 2013; Donnelly et al, 2013; Sareen et al, 2013), in which several aspects of C9ORF72-related pathology were observed
Summary
Amyotrophic Lateral SclerosisAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the selective death of both upper and lower motor neurons (Renton et al, 2014). SOD1 In 2014, two back-to-back studies were published which used novel in vitro models for ALS by generating iPSC-derived motor neurons from patients carrying a SOD1A4V or a SOD1D90A mutation (Chen et al, 2014; Kiskinis et al, 2014). These motor neurons recapitulated the spontaneous and progressive decrease in cell viability observed in humans
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