Modeling Parkinson's Disease Using Patient-specific Induced Pluripotent Stem Cells

Journal of Parkinson's Disease
Hong LiJian Feng

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is characterized by the degeneration of nigral dopaminergic (DA) neurons. While over 90% of cases are idiopathic, without a clear etiology, mutations in many genes have been linked to rare, familial forms of PD. It has been quite challenging to develop effective animal models of PD that capture salient features of PD. The discovery of induced pluripotent stem cells (iPSCs) makes it possible to generate patient-specific DA neurons to study PD. Here, we review the methods for the generation of iPSCs and discuss previous studies using iPSC-derived neurons from monogenic forms of PD. These investigations have revealed several converging pathways that intersect with the unique vulnerabilities of human nigral DA neurons. With the rapid development in stem cell biology, it is possible to generate patient-specific neurons that will be increasingly similar to those in the brain of the patient. Combined with the ability to edit the genome to generate isogenic iPSCs, the generation and analysis of patient-specific midbrain DA neurons will transform PD research by providing a valuable tool for mechanistic study and drug discovery.

References

Mar 21, 1996·Nature·D M GashG A Gerhardt
Aug 1, 1996·Current Biology : CB·M A Frohman, A J Morris
Aug 28, 1997·Nature·M G SpillantiniM Goedert
Apr 15, 1999·Annual Review of Neuroscience·J C ShihM J Ridd
May 29, 2000·The New England Journal of Medicine·C B LückingUNKNOWN European Consortium on Genetic Susceptibility in Parkinson's Disease
May 2, 2001·Nature Reviews. Neuroscience·M F Beal
Jul 27, 2001·Current Opinion in Neurology·M VilaS Przedborski
Sep 18, 2001·Annals of Neurology·M FarrerJ W Langston
Nov 13, 2002·Biochemistry·Thomas D KimChul-Hak Yang
Aug 22, 2003·The Journal of Biological Chemistry·Matthew S GoldbergJie Shen
Nov 1, 2003·Science·A B SingletonK Gwinn-Hardy
Apr 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sylvia N SchreiberAnastasia Kralli
Jun 17, 2004·Human Molecular Genetics·Houbo JiangJian Feng
Dec 14, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Leonid YavichPekka Jäkälä
Feb 3, 2005·Proceedings of the National Academy of Sciences of the United States of America·Francisco A Perez, Richard D Palmiter
Feb 4, 2006·The Journal of Biological Chemistry·Houbo JiangJian Feng
Feb 21, 2006·Lancet Neurology·K Ray ChaudhuriUNKNOWN National Institute for Clinical Excellence
Nov 3, 2006·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Jian Feng
Nov 23, 2006·Neuron·David MacLeodAsa Abeliovich
Jun 1, 2007·Neurobiology of Aging·Xiaomin SuHoward J Federoff
Jan 10, 2008·Journal of Neurochemistry·Edward D PloweyCharleen T Chu
May 1, 2008·Experimental Cell Research·Narae ShinWongi Seol
Nov 26, 2008·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Maria A Mena, Justo García de Yébenes
Nov 26, 2008·The Journal of Cell Biology·Derek NarendraRichard J Youle
Jan 16, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Wakoto MatsudaTakeshi Kaneko
Sep 4, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jaime N GuzmanD James Surmeier
Sep 24, 2009·BMC Medical Genetics·Jeanne C LatourelleUNKNOWN GenePD Investigators, Coordinators and Molecular Genetic Laboratories
Oct 20, 2009·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Noemi FusakiMamoru Hasegawa
Nov 6, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Loukia ParisiadouHuaibin Cai
Feb 9, 2010·Nature Methods·Fangjun JiaJoseph C Wu

❮ Previous
Next ❯

Citations

Jun 5, 2019·Future Medicinal Chemistry·Juan Antonio Garcia-LeonAntonia Gutierrez
Feb 7, 2020·SLAS Discovery·Ami KabadiLauren Drowley
Feb 13, 2020·Current Protocols in Neuroscience·Mikko AiravaaraAndrii Domanskyi
Aug 24, 2019·Current Stem Cell Research & Therapy·Tannaz Akbari KolagarSeyed Esmaeil Khoshnam
Nov 27, 2019·Cold Spring Harbor Perspectives in Biology·Krishna C VadodariaFred H Gage
Aug 6, 2020·International Journal of Molecular Sciences·Daniela Gois BeghiniAndrea Henriques-Pons
Jul 7, 2020·Frontiers in Cell and Developmental Biology·Tiago Cardoso, Martin Lévesque
Oct 17, 2019·World Journal of Stem Cells·Minjing KeHuanxing Su
Oct 23, 2019·Neural Regeneration Research·Rubaiya TabassumJunyang Jung
Sep 24, 2020·NPJ Parkinson's Disease·Steven E PierceGerhard A Coetzee
Oct 6, 2020·Frontiers in Neurology·Benjamin GaletPhilippe Ravassard
Mar 12, 2020·Bulletin of Experimental Biology and Medicine·E A CherkashovaK N Yarygin
Oct 7, 2020·Brain : a Journal of Neurology·Polyxeni NikolakopoulouAnna Herland
Apr 4, 2021·Brain Sciences·Sahar AvazzadehLeo R Quinlan
May 1, 2021·Stem Cell Research & Therapy·Elena Coccia, Tim Ahfeldt
Jul 3, 2021·Biomolecules·Oliwia KoszłaAgnieszka A Kaczor

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPase
deamination

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.

Amygdala and Midbrain Dopamine

The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.