Corrigendum: SLP-2 interacts with Parkin in mitochondria and prevents mitochondrial dysfunction in Parkin-deficient human iPSC-derived neurons and <i>Drosophila</i>

Zanon, Alessandra; Kalvakuri, Sreehari; Raković, Aleksandar; Foco, Luisa; Guida, Marianna; Schwienbacher, Christine; Serafin, Alice; Rudolph, Franziska; Trilck, Michaela; Grünewald, Anne; Stanslowsky, Nancy; Wegner, Florian; Giorgio, Valentina; Lavdas, Alexandros A.; Bodmer, Rolf; Pramstaller, Peter P.; Klein, Christine; Hicks, Andrew A.; Pichler, Irene; Philip, Susan Mary

doi:10.1093/hmg/ddy408

Cited by 13 publications

(17 citation statements)

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“…To determine whether our findings are evolutionary conserved, we generated induced human hypothalamic neurons ( Figure S4A; Merkle et al, 2015). We used two patient-derived iPSCs carrying parkin mutations, two patients with pink1 mutations, and two age-matched individuals without Parkinson's disease ( Figure S4B; Seibler et al, 2011;Zanon et al, 2017). We confirmed that these four patients suffered from sleep disturbances, whereas the control individuals had no complaints ( Figure S4B).…”

Section: Neuropeptides Are Arrested In Neuronal Cell Bodies Of Parkinmentioning

confidence: 71%

“…iPSC maintenance and differentiation iPSC from 2 parkin patients with gene deletions and point mutations (lines L3048, male; and L5415, female), 2 PINK1 patients with a premature STOP codon (lines L2124 and L2126, both females) as well as 2 matched controls (lines L4993 and L5991, both females, Figure S4B, Seibler et al, 2011;Zanon et al, 2017) were differentiated into hypothalamic neurons according to a protocol described before (Merkle et al, 2015). Briefly, cells were maintained in matrigel coated plates with mTeSR1 (Stem Cell Technologies) and medium changes were performed every two days.…”

Section: Star+methodsmentioning

confidence: 99%

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ER Lipid Defects in Neuropeptidergic Neurons Impair Sleep Patterns in Parkinson’s Disease

Valadas

Esposito

Vandekerkhove

et al. 2018

Neuron

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101

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Parkinson's disease patients report disturbed sleep patterns long before motor dysfunction. Here, in parkin and pink1 models, we identify circadian rhythm and sleep pattern defects and map these to specific neuropeptidergic neurons in fly models and in hypothalamic neurons differentiated from patient induced pluripotent stem cells (iPSCs). Parkin and Pink1 control the clearance of mitochondria by protein ubiquitination. Although we do not observe major defects in mitochondria of mutant neuropeptidergic neurons, we do find an excess of endoplasmic reticulum-mitochondrial contacts. These excessive contact sites cause abnormal lipid trafficking that depletes phosphatidylserine from the endoplasmic reticulum (ER) and disrupts the production of neuropeptide-containing vesicles. Feeding mutant animals phosphatidylserine rescues neuropeptidergic vesicle production and acutely restores normal sleep patterns in mutant animals. Hence, sleep patterns and circadian disturbances in Parkinson's disease models are explained by excessive ER-mitochondrial contacts, and blocking their formation or increasing phosphatidylserine levels rescues the defects in vivo.

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Section: Neuropeptides Are Arrested In Neuronal Cell Bodies Of Parkinmentioning

confidence: 71%

Section: Star+methodsmentioning

confidence: 99%

ER Lipid Defects in Neuropeptidergic Neurons Impair Sleep Patterns in Parkinson’s Disease

Valadas

Esposito

Vandekerkhove

et al. 2018

Neuron

Self Cite

101

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“…In summary, alterations in mitochondrial morphology were repeatedly shown not only for LRRK2 variants (Su & Qi, ) but also for mutants of SNCA trp/A53T PINK1, PRKN and OPA1 (Chung et al., ; Iannielli et al., ; Imaizumi et al., ; Little et al., ; Shaltouki et al., ; Zanon et al., ).…”

Section: Pd‐associated Lrrk2 Variants In Ipsc‐based Disease Modelingmentioning

confidence: 90%

Induced pluripotent stem cell‐based modeling of mutant LRRK2‐associated Parkinson's disease

Weykopf

Haupt

Jungverdorben

et al. 2019

Eur J of Neuroscience

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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.

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“…[82][83][84][85] Besides the role of PINK1, Parkin and DJ1 in mitophagy and Ca 2+ dynamics, these proteins also modulate the function of the mitochondrial respiratory chain complex. 86 Mutations in these genes disrupt the assembly of the components of the respiratory chain complex, inhibit complexes I and III, and increase the generation of ROS and reactive nitrogen species (RNS).…”

Section: Mitochondrial Maintenancementioning

confidence: 99%

Progress in the molecular pathogenesis and nucleic acid therapeutics for Parkinson's disease in the precision medicine era

Mastaglia

Fletcher

et al. 2020

Medicinal Research Reviews

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Parkinson's disease (PD) is one of the most common neurodegenerative disorders that manifest various motor and nonmotor symptoms. Although currently available therapies can alleviate some of the symptoms, the disease continues to progress, leading eventually to severe motor and cognitive decline and reduced life expectancy. The past two decades have witnessed rapid progress in our understanding of the molecular and genetic pathogenesis of the disease, paving the way for the development of new therapeutic approaches to arrest or delay the neurodegenerative process. As a result of these advances, biomarker-driven subtyping is making it possible to stratify PD patients into more homogeneous subgroups that may better respond to potential genetic-molecular pathway targeted disease-modifying therapies. Therapeutic nucleic acid oligomers can bind to target gene sequences with very high specificity in a base-pairing manner and precisely modulate downstream molecular events. Recently, nucleic acid therapeutics have proven effective in the treatment of a number of severe neurological and neuromuscular disorders, drawing increasing attention to the possibility of developing novel molecular therapies for PD. In this

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Corrigendum: SLP-2 interacts with Parkin in mitochondria and prevents mitochondrial dysfunction in Parkin-deficient human iPSC-derived neurons and Drosophila

Cited by 13 publications

References 0 publications

ER Lipid Defects in Neuropeptidergic Neurons Impair Sleep Patterns in Parkinson’s Disease

ER Lipid Defects in Neuropeptidergic Neurons Impair Sleep Patterns in Parkinson’s Disease

Induced pluripotent stem cell‐based modeling of mutant LRRK2‐associated Parkinson's disease

Progress in the molecular pathogenesis and nucleic acid therapeutics for Parkinson's disease in the precision medicine era

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