Human Pluripotent Stem Cell-Derived Neural Cells as a Relevant Platform for Drug Screening in Alzheimer’s Disease

Autor: Garcia-Leon, Juan Antonio, Caceres-Palomo, Laura, Sanchez-Mejias, Elisabeth, Mejias-Ortega, Marina, Nuñez-Diaz, Cristina, Fernandez-Valenzuela, Juan Jose, Sanchez-Varo, Raquel, Davila, Jose Carlos, Vitorica, Javier, Gutierrez, Antonia
Přispěvatelé: Instituto de Salud Carlos III, European Commission, Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España), Junta de Andalucía, Universidad de Málaga, Ministerio de Ciencia, Innovación y Universidades (España), [Garcia-Leon,JA, Caceres-Palomo,L, Sanchez-Mejias,E, Mejias-Ortega,M, Nuñez-Diaz,C, Fernandez-Valenzuela,JJ, Sanchez-Varo,R, Davila,JC, Gutierrez,A] Departamento Biologia Celular, Genetica y Fisiologia, Instituto de Investigacion Biomedica de Malaga-IBIMA, Facultad de Ciencias, Universidad de Malaga, Malaga, Spain. [Garcia-Leon,JA, Vitorica,J, Gutierrez,A] Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. [Vitorica,J] Departamento Bioquimica y Biologia Molecular, Facultad de Farmacia, Universidad de Sevilla, Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Sevilla, Spain., This study was supported by Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union, through grants PI18/01557 (to AG), PI18/01556 (to JV), and CIBERNED (CB06/05/1116 to AG and CB06/05/0094 to JV), by Junta de Andalucia through Consejería de Economía y Conocimiento grants UMA18-FEDERJA-211 (to AG), PY18-RT-2233 (to AG) and US-1262734 (to JV) co-financed by Programa Operativo FEDER 2014-2020 and Consejeria de Salud grant PI-0276-2018 (to JAGL), and by Malaga University grant PPIT.UMA.B1.2017/26 (to RSV). JJFV was supported by an FPU PhD fellowship from Spanish Ministry of Science, Innovation, and Universities, and RSV and MMO held a postdoctoral and predoctoral contract, respectively, from Malaga University.
Rok vydání: 2020
Předmět:
Astrocitos
Analytical
Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Culture Techniques::Cell Culture Techniques [Medical Subject Headings]

Diseases::Nervous System Diseases::Neurodegenerative Diseases::Tauopathies::Alzheimer Disease [Medical Subject Headings]
Organoides
Anatomy::Cells::Neuroglia::Oligodendroglia [Medical Subject Headings]
Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings]
Brain organoids
Enfermedad de Alzheimer
Anatomy::Cells::Neuroglia::Microglia [Medical Subject Headings]
Anatomy::Cells::Stem Cells::Neural Stem Cells [Medical Subject Headings]
Human induced pluripotent stem cells (hiPSCs)
Anatomy::Cells::Stem Cells::Pluripotent Stem Cells::Induced Pluripotent Stem Cells [Medical Subject Headings]
3D cultures
Oligodendrocytes
Analytical
Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug Discovery::Drug Evaluation
Preclinical [Medical Subject Headings]

Anatomy::Cells::Neuroglia::Astrocytes [Medical Subject Headings]
Anatomy::Tissues::Organoids [Medical Subject Headings]
Chemicals and Drugs::Amino Acids
Peptides
and Proteins::Peptides::Amyloid beta-Peptides [Medical Subject Headings]

Células madre pluripotentes inducidas
Disease modeling
Oligodendroglía
Astrocytes
Microglía
Microglia
Chemicals and Drugs::Amino Acids
Peptides
and Proteins::Proteins::Nerve Tissue Proteins::Microtubule-Associated Proteins::tau Proteins [Medical Subject Headings]

Alzheimer’s disease
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
Popis: This article belongs to the Special Issue hiPSC-Derived Cells as Models for Drug Discovery. Extracellular amyloid-beta deposition and intraneuronal Tau-laden neurofibrillary tangles are prime features of Alzheimer’s disease (AD). The pathology of AD is very complex and still not fully understood, since different neural cell types are involved in the disease. Although neuronal function is clearly deteriorated in AD patients, recently, an increasing number of evidences have pointed towards glial cell dysfunction as one of the main causative phenomena implicated in AD pathogenesis. The complex disease pathology together with the lack of reliable disease models have precluded the development of effective therapies able to counteract disease progression. The discovery and implementation of human pluripotent stem cell technology represents an important opportunity in this field, as this system allows the generation of patient-derived cells to be used for disease modeling and therapeutic target identification and as a platform to be employed in drug discovery programs. In this review, we discuss the current studies using human pluripotent stem cells focused on AD, providing convincing evidences that this system is an excellent opportunity to advance in the comprehension of AD pathology, which will be translated to the development of the still missing effective therapies. This study was supported by Instituto de Salud Carlos III (ISCiii) of Spain, co-financed by FEDER funds from European Union, through grants PI18/01557 (to AG), PI18/01556 (to JV), and CIBERNED (CB06/05/1116 to AG and CB06/05/0094 to JV); by Junta de Andalucia through Consejería de Economía y Conocimiento grants UMA18-FEDERJA-211 (to AG), PY18-RT-2233 (to AG) and US-1262734 (to JV) co-financed by Programa Operativo FEDER 2014-2020 and Consejeria de Salud grant PI-0276-2018 (to JAGL); and by Malaga University grant PPIT.UMA.B1.2017/26 (to RSV). JJFV was supported by an FPU PhD fellowship from Spanish Ministry of Science, Innovation, and Universities, and RSV and MMO held a postdoctoral and predoctoral contract, respectively, from Malaga University.
Databáze: OpenAIRE