title: Human pluripotent stem cells as tools for neurodegenerative and neurodevelopmental disease modeling and drug discovery.
abstract: BACKGROUND
  Although intensive efforts have been made, effective treatments for neurodegenerative and neurodevelopmental diseases have not been yet discovered. Possible reasons for this include the lack of appropriate disease models of human neurons and a limited understanding of the etiological and neurobiological mechanisms. Recent advances in pluripotent stem cell (PSC) research have now opened the path to the generation of induced pluripotent stem cells (iPSCs) starting from somatic cells, thus offering an unlimited source of patient-specific disease-relevant neuronal cells.
  
  
  METHODS
  In this review, the authors focus on the use of human PSC-derived cells in modeling neurological disorders and discovering of new drugs and provide their expert perspectives on the field.
  
  
  CONCLUSIONS
  The advent of human iPSC-based disease models has fuelled renewed enthusiasm and enormous expectations for insights of disease mechanisms and identification of more disease-relevant and novel molecular targets. Human PSCs offer a unique tool that is being profitably exploited for high-throughput screening (HTS) platforms. This process can lead to the identification and optimization of molecules/drugs and thus move forward new pharmacological therapies for a wide range of neurodegenerative and neurodevelopmental conditions. It is predicted that improvements in the production of mature neuronal subtypes, from patient-specific human-induced pluripotent stem cells and their adaptation to culture, to HTS platforms will allow the increased exploitation of human pluripotent stem cells in drug discovery programs.
authors.affiliation: University of Milan, Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation, Neurology Unit, IRCCS Foundation Ca'Granda Ospedale Maggiore Policlinico , via Francesco Sforza 35, Milan 20122 , Italy +39 02 55033817 ; Stefania.Corti@unimi.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
authors.forename: Irene
authors.initials: I
authors.lastname: Faravelli
authors.forename: Marina
authors.initials: M
authors.lastname: Cardano
authors.forename: Luciano
authors.initials: L
authors.lastname: Conti
mesh_terms: D000818:Animals; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D057166:High-Throughput Screening Assays; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000503:physiopathology*; D065886:Neurodevelopmental Disorders / Q000188:drug therapy / Q000503:physiopathology*; D039904:Pluripotent Stem Cells / Q000166:cytology*
keywords: cell-based drug screening; disease modeling; drug discovery; human ES cells; human iPS cells; neurodegenerative diseases; neurodevelopmental disorders; neuronal subtypes; screening platforms