2020
DOI: 10.3389/fneur.2020.01005
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Patient-Derived Midbrain Organoids to Explore the Molecular Basis of Parkinson's Disease

Abstract: Induced pluripotent stem cell-derived organoids offer an unprecedented access to complex human tissues that recapitulate features of architecture, composition and function of in vivo organs. In the context of Parkinson's Disease (PD), human midbrain organoids (hMO) are of significant interest, as they generate dopaminergic neurons expressing markers of Substantia Nigra identity, which are the most vulnerable to degeneration. Combined with genome editing approaches,… Show more

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Cited by 31 publications
(23 citation statements)
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References 173 publications
(257 reference statements)
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“…LRRK2 encodes the leucine-rich repeat serine/threonine-protein kinase 2. LRRK2 is an incompletely penetrant gene associated with increased PD risk ( 116 , 117 ). The LRRK2-G2019S mutation has a variable penetrance and is associated with both sporadic and familial PD.…”
Section: Microglia and Their Role In Parkinson's Diseasementioning
confidence: 99%
“…LRRK2 encodes the leucine-rich repeat serine/threonine-protein kinase 2. LRRK2 is an incompletely penetrant gene associated with increased PD risk ( 116 , 117 ). The LRRK2-G2019S mutation has a variable penetrance and is associated with both sporadic and familial PD.…”
Section: Microglia and Their Role In Parkinson's Diseasementioning
confidence: 99%
“…LRRK2-G2019S, a missense mutation in the leucine-rich repeat kinase 2 (LRRK2) gene locus, is primarily associated with alpha-synuclein accumulation and mitochondrial dysfunction and represents the most commonly known cause of late-onset familial and sporadic PD. Several reports showed that disease-relevant phenotypes in PD patients, including increased aggregation of alphasynuclein and its aberrant clearance, were recapitulated in 3D culture, closely mimicking those seen in patients with mutant LRRK2-associated sporadic PD (Figure 2C) [73,81,82].…”
Section: D Culturementioning
confidence: 69%
“…showed that disease-relevant phenotypes in PD patients, including increased aggregat of alpha-synuclein and its aberrant clearance, were recapitulated in 3D culture, clos mimicking those seen in patients with mutant LRRK2-associated sporadic PD (Figure [73,81,82]. However, the remarkable potential of brain organoids to model later developmen stages and generate more mature neurons has to date been hampered by their poor rep ducibility and incomplete maturation.…”
Section: D Culturementioning
confidence: 95%
“…In the sequential patterning, dual SMAD inhibitors (dorsomorphin, SB431542, LDN193189, A83, NOG) were used along with WNT modulation (CHIR99021) for the midbrain specification step, followed by midbrain floor plate induction using SHH modulation (smoothened agonist, SHH, purmorphamine) and FGF8, and finally, differentiation and maturation using neurotropic factors BDNF and brain-derived neurotropic factor (GDNF). In simultaneous patterning protocol, the midbrain specification and floor plate induction steps were combined together, followed by maturation step similar to sequential method but involving additional supplements (FGF20, TGFβ3, trichostatin A) (Smits and Schwamborn 2020 ; Galet et al 2020 ).…”
Section: Current Organoid Culture Strategiesmentioning
confidence: 99%
“…Parkinson’s disease (PD) is caused due to accumulation of Lewy bodies that lead to selective degeneration of dopaminergic neurons. PD can be studied by modeling of midbrain organoids (Smits and Schwamborn 2020 ; Galet et al 2020 ). Animal models used to study the brain development and function in neuropsychiatric diseases fail to match the human brain system.…”
Section: Application Of Organoids In Human Health and Diseasementioning
confidence: 99%