Multiple system atrophy (MSA) is a rare neurodegenerative disease with a fatal outcome. Nowadays, only symptomatic treatment is available for MSA patients. The hallmarks of the disease are glial cytoplasmic inclusions (GCIs), proteinaceous aggregates mainly composed of alpha-synuclein, which accumulate in oligodendrocytes. However, despite the extensive research efforts, little is known about the pathogenesis of MSA. Early myelin dysfunction and alpha-synuclein deposition are thought to play a major role, but the origin of the aggregates and the causes of misfolding are obscure. One of the reasons for this is the lack of a reliable model of the disease. Recently, the development of induced pluripotent stem cell (iPSC) technology opened up the possibility of elucidating disease mechanisms in neurodegenerative diseases including MSA. Patient specific iPSC can be differentiated in glia and neurons, the cells involved in MSA, providing a useful human disease model. Here, we firstly review the progress made in MSA modelling with primary cell cultures. Subsequently, we focus on the first iPSC-based model of MSA, which showed that alpha-synuclein is expressed in oligodendrocyte progenitors, whereas its production decreases in mature oligodendrocytes. We then highlight the opportunities offered by iPSC in studying disease mechanisms and providing innovative models for testing therapeutic strategies, and we discuss the challenges connected with this technique.
In vitro models of multiple system atrophy from primary cells to induced pluripotent stem cells / E. Abati, A. Di Fonzo, S. Corti. - In: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE. - ISSN 1582-1838. - 22:5(2018 Mar 04), pp. 2536-2546.
|Titolo:||In vitro models of multiple system atrophy from primary cells to induced pluripotent stem cells|
|Parole Chiave:||induced pluripotent stem cells; in vitro models; multiple system atrophy; neurodegeneration; oligodendrocytes|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
|Data di pubblicazione:||4-mar-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/jcmm.13563|
|Appare nelle tipologie:||01 - Articolo su periodico|
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