Home > Publications Database > Induced pluripotent stem cell-based modeling of mutant LRRK2-associated Parkinson's disease. > print

001     140517
005     20240321220826.0
024 7 _ |a pmc:PMC7114274
|2 pmc
024 7 _ |a 10.1111/ejn.14345
|2 doi
024 7 _ |a pmid:30656775
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024 7 _ |a 0953-816X
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024 7 _ |a 1460-9568
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037 _ _ |a DZNE-2020-06839
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Weykopf, Beatrice
|0 P:(DE-HGF)0
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245 _ _ |a Induced pluripotent stem cell-based modeling of mutant LRRK2-associated Parkinson's disease.
260 _ _ |a Oxford [u.a.]
|c 2019
|b Blackwell
264 _ 1 |3 print
|2 Crossref
|b Wiley
|c 2019-02-01
336 7 _ |a article
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336 7 _ |a Output Types/Journal article
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336 7 _ |a Journal Article
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336 7 _ |a Journal Article
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520 _ _ |a Recent advances in cell reprogramming have enabled assessment of disease-related cellular traits in patient-derived somatic cells, thus providing a versatile platform for disease modeling and drug development. Given the limited access to vital human brain cells, this technology is especially relevant for neurodegenerative disorders such as Parkinson's disease (PD) as a tool to decipher underlying pathomechanisms. Importantly, recent progress in genome-editing technologies has provided an ability to analyze isogenic induced pluripotent stem cell (iPSC) pairs that differ only in a single genetic change, thus allowing a thorough assessment of the molecular and cellular phenotypes that result from monogenetic risk factors. In this review, we summarize the current state of iPSC-based modeling of PD with a focus on leucine-rich repeat kinase 2 (LRRK2), one of the most prominent monogenetic risk factors for PD linked to both familial and idiopathic forms. The LRRK2 protein is a primarily cytosolic multi-domain protein contributing to regulation of several pathways including autophagy, mitochondrial function, vesicle transport, nuclear architecture and cell morphology. We summarize iPSC-based studies that contributed to improving our understanding of the function of LRRK2 and its variants in the context of PD etiopathology. These data, along with results obtained in our own studies, underscore the multifaceted role of LRRK2 in regulating cellular homeostasis on several levels, including proteostasis, mitochondrial dynamics and regulation of the cytoskeleton. Finally, we expound advantages and limitations of reprogramming technologies for disease modeling and drug development and provide an outlook on future challenges and expectations offered by this exciting technology.
536 _ _ |a 344 - Clinical and Health Care Research (POF3-344)
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542 _ _ |i 2019-02-25
|2 Crossref
|u http://creativecommons.org/licenses/by-nc/4.0/
542 _ _ |i 2019-02-01
|2 Crossref
|u http://doi.wiley.com/10.1002/tdm_license_1.1
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Induced Pluripotent Stem Cells
|2 MeSH
650 _ 2 |a Leucine-Rich Repeat Serine-Threonine Protein Kinase-2: genetics
|2 MeSH
650 _ 2 |a Mitophagy
|2 MeSH
650 _ 2 |a Models, Neurological
|2 MeSH
650 _ 2 |a Parkinson Disease: genetics
|2 MeSH
650 _ 2 |a Parkinson Disease: therapy
|2 MeSH
700 1 _ |a Haupt, Simone
|b 1
700 1 _ |a Jungverdorben, Johannes
|0 P:(DE-HGF)0
|b 2
700 1 _ |a Flitsch, Lea Jessica
|b 3
700 1 _ |a Hebisch, Matthias
|0 P:(DE-HGF)0
|b 4
700 1 _ |a Liu, Guang-Hui
|b 5
700 1 _ |a Suzuki, Keiichiro
|b 6
700 1 _ |a Belmonte, Juan Carlos Izpisua
|b 7
700 1 _ |a Peitz, Michael
|0 P:(DE-2719)9000249
|b 8
|u dzne
700 1 _ |a Blaess, Sandra
|b 9
700 1 _ |a Till, Andreas
|0 P:(DE-HGF)0
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|e Corresponding author
700 1 _ |a Brüstle, Oliver
|0 P:(DE-HGF)0
|b 11
773 1 8 |a 10.1111/ejn.14345
|b : Wiley, 2019-02-01
|n 4
|p 561-589
|3 journal-article
|2 Crossref
|t European Journal of Neuroscience
|v 49
|y 2019
|x 0953-816X
773 _ _ |a 10.1111/ejn.14345
|g Vol. 49, no. 4, p. 561 - 589
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|q 49:4<561 - 589
|p 561-589
|t European journal of neuroscience
|v 49
|y 2019
|x 0953-816X
909 C O |o oai:pub.dzne.de:140517
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914 1 _ |y 2019
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LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21