ArticleNature medicine2020
iPSC modeling of young-onset Parkinson's disease reveals a molecular signature of disease and novel therapeutic candidates.
Article in Nature medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 of them syntheses that pooled it.
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Who cites it
73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 125 citations in OpenAlex.
- The DJ1-Nrf2-STING axis mediates the neuroprotective effects of Withaferin A in Parkinson's disease.Cell death and differentiation · 2021Pooled it
- Building on a Solid Foundation: Adding Relevance and Reproducibility to Neurological Modeling Using Human Pluripotent Stem Cells.Frontiers in cellular neuroscience · 2021Pooled it
- Brain organoids as models of extracellular vesicle-mediated human neural communication.Neural regeneration research · 2026Article
- From neural loss to regeneration: modulating cell death to enhance pluripotent stem cell graft survival and integration.Cell death & disease · 2026Review
- Autophagy dysfunction in iPSCs-derived neurons and midbrain organoids carrying a SNCA triplication.NPJ Parkinson's disease · 2026Article
- Neurogenesis defects in iPSC-derived midbrain organoids of early-onset Parkinson's disease with 22q11.2 deletion syndrome.Frontiers in cellular neuroscience · 2026Article
- Effects of esketamine on electrophysiology and metabolic reprogramming in brain organoids: insights into antidepressant mechanisms.Molecular psychiatry · 2025Article
- Morphological profiling reveals neuroprotection via mitochondrial uncoupling in human dopaminergic neurons.Scientific reports · 2025Article
- Advances, challenges, and opportunities of human midbrain organoids for modelling of the dopaminergic system.The EMBO journal · 2025Review
- An organ-chip model of sporadic ALS using iPSC-derived spinal cord motor neurons and an integrated blood-brain-like barrier.Cell stem cell · 2025Article
- Ergothioneine Treatment Ameliorates the Pathological Phenotypes of Parkinson's Disease Models.Journal of neurochemistry · 2025Article
- Identification of Common Brain Protein and Genetic Loci Between Parkinson's Disease and Lewy Body Dementia.CNS neuroscience & therapeutics · 2025Article
- Microfluidic tools to model, monitor, and modulate the gut-brain axis.Biomicrofluidics · 2025Article
- Stem Cell-Based Approaches in Parkinson's Disease Research.International journal of stem cells · 2025Review
- Review
- A review of regenerative medicine and tissue engineering with a focus on wound healing and anti-aging.Frontiers in surgery · 2025Review
- The Neuroanatomy of Induced Pluripotent Stem Cells: In Vitro Models of Subcortical Nuclei in Neurodegenerative Disorders.Current issues in molecular biology · 2024Review
- RXR nuclear receptor signaling modulates lipid metabolism and triggers lysosomal clearance of alpha-synuclein in neuronal models of synucleinopathy.Cellular and molecular life sciences : CMLS · 2024Article
- Replacing Animal Testing with Stem Cell-Organoids : Advantages and Limitations.Stem cell reviews and reports · 2024Review
- In and out: Benchmarking in vitro, in vivo, ex vivo, and xenografting approaches for an integrative brain disease modeling pipeline.Stem cell reports · 2024Review
13 more citing papers are in PubMed but not listed here.
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18 authors at 3 institutions in 2 countries.
Funding
Abstract
Young-onset Parkinson's disease (YOPD), defined by onset at <50 years, accounts for approximately 10% of all Parkinson's disease cases and, while some cases are associated with known genetic mutations, most are not. Here induced pluripotent stem cells were generated from control individuals and from patients with YOPD with no known mutations. Following differentiation into cultures containing dopamine neurons, induced pluripotent stem cells from patients with YOPD showed increased accumulation of soluble α-synuclein protein and phosphorylated protein kinase Cα, as well as reduced abundance of lysosomal membrane proteins such as LAMP1. Testing activators of lysosomal function showed that specific phorbol esters, such as PEP005, reduced α-synuclein and phosphorylated protein kinase Cα levels while increasing LAMP1 abundance. Interestingly, the reduction in α-synuclein occurred through proteasomal degradation. PEP005 delivery to mouse striatum also decreased α-synuclein production in vivo. Induced pluripotent stem cell-derived dopaminergic cultures reveal a signature in patients with YOPD who have no known Parkinson's disease-related mutations, suggesting that there might be other genetic contributions to this disorder. This signature was normalized by specific phorbol esters, making them promising therapeutic candidates.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.