iPSC-Based Models to Unravel Key Pathogenetic Processes Underlying Motor Neuron Disease Development

Journal of Clinical Medicine

Irene Faravelli¹  Emanuele Frattini¹  Agnese Ramirez²  Giulia Stuppia²  Monica Nizzardo²  Stefania Corti¹ 

[1] Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Neurology Unit, IRCCS Foundation Ca’Granda Ospedale Maggiore Policlinico, via Francesco Sforza 35, 20122 Milan, Italy;

关键词: induced pluripotent stem cells;    amyotrophic lateral sclerosis;    spinal muscular atrophy;    disease modeling;   

DOI  :  10.3390/jcm3041124

来源: mdpi

【 摘 要 】

Motor neuron diseases (MNDs) are neuromuscular disorders affecting rather exclusively upper motor neurons (UMNs) and/or lower motor neurons (LMNs). The clinical phenotype is characterized by muscular weakness and atrophy leading to paralysis and almost invariably death due to respiratory failure. Adult MNDs include sporadic and familial amyotrophic lateral sclerosis (sALS-fALS), while the most common infantile MND is represented by spinal muscular atrophy (SMA). No effective treatment is ccurrently available for MNDs, as for the vast majority of neurodegenerative disorders, and cures are limited to supportive care and symptom relief. The lack of a deep understanding of MND pathogenesis accounts for the difficulties in finding a cure, together with the scarcity of reliable in vitro models. Recent progresses in stem cell field, in particular in the generation of induced Pluripotent Stem Cells (iPSCs) has made possible for the first time obtaining substantial amounts of human cells to recapitulate in vitro some of the key pathogenetic processes underlying MNDs. In the present review, recently published studies involving the use of iPSCs to unravel aspects of ALS and SMA pathogenesis are discussed with an overview of their implications in the process of finding a cure for these still orphan disorders.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.