ArticleCell stem cell2023
Advanced human iPSC-based preclinical model for Parkinson's disease with optogenetic alpha-synuclein aggregation.
Article in Cell stem cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 49 citations in OpenAlex.
- A Live-Cell Imaging System for the Identification of Pro- and Anti-Aggregatory α-Synuclein Modulators.Molecular neurobiology · 2026Article
- Organoids: Key advances, optimization, and technological iterations in their application to neurodegenerative diseases.Neural regeneration research · 2026Article
- Stem cell derived neural organoid approaches for neurological diseases.Neural regeneration research · 2026Article
- Developmentally Guided Differentiation of Ventral Midbrain Dopaminergic Cells Validated in Proteopathy-Based Parkinson's Disease Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Atorvastatin Shows Limited Disease-Modifying Effects in an A53T α-Synuclein Mouse Model of Parkinson's Disease.Neurotoxicity research · 2026Article
- Beyond phenotypic markers: rethinking dopaminergic identity in iPSC-derived neurons.Cell communication and signaling : CCS · 2026Review
- Modeling Parkinson's pathology in human iPSC dopaminergic neurons uncovers key mechanisms of Lewy body formation and heterogeneity.Science advances · 2026Article
- Curcumin Attenuates Cuproptosis via Activating Autophagy Through Inhibition of the AKT/mTOR/P70S6K-Signaling Pathway in Parkinson's Disease Models.Molecular neurobiology · 2026Article
- Inter-organ communication shapes human metabolic tissue states and resolves anti-diabetic drug response modes in a six-tissue microphysiological system.bioRxiv : the preprint server for biology · 2026Article
- Review
- Stem Cell-Derived Exosomes Regulate Mitochondrial Function: A Novel Strategy for Parkinson's Disease Therapy.Molecular neurobiology · 2026Review
- CRISPR Applications in Alzheimer's Disease: From High-Throughput Genetic Screening to Precision Editing and CNS Delivery.International journal of molecular sciences · 2026Review
- Modelling synaptic dysfunction in childhood dementia using human iPSC-derived cortical networks.Nature communications · 2026Article
- Review
- Human pluripotent stem cell engineering with CRISPR-Cas9 for Parkinson's disease.Experimental & molecular medicine · 2026Review
- Copper Dyshomeostasis Affects α-Synuclein Clearance Mechanisms in Parkinson's Disease: Insights from In Vitro Models and Translational Evidence.International journal of molecular sciences · 2026Review
- Brain organoids as precision models for neurodegenerative diseases: from disease modeling to drug discovery.Frontiers in neuroscience · 2026Review
- Differentiation of human iPSCs into dopaminergic neurons: comparative analysis of 2D and 3D protocols for disease modeling and pharmacology.Neuroscience applied · 2026Review
- Japanese encephalitis virus activates the NLRP3/caspase-1/GSDMD signaling pathway in dopaminergic neurons.PLoS neglected tropical diseases · 2026Article
- Temporal Transcriptional Regulation of Human Neuronal Differentiation via Forward Programming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Human induced pluripotent stem cells (hiPSCs) offer advantages for disease modeling and drug discovery. However, recreating innate cellular pathologies, particularly in late-onset neurodegenerative diseases with accumulated protein aggregates including Parkinson's disease (PD), has been challenging. To overcome this barrier, we developed an optogenetics-assisted α-synuclein (α-syn) aggregation induction system (OASIS) that rapidly induces α-syn aggregates and toxicity in PD hiPSC-midbrain dopaminergic neurons and midbrain organoids. Our OASIS-based primary compound screening with SH-SY5Y cells identified 5 candidates that were secondarily validated with OASIS PD hiPSC-midbrain dopaminergic neurons and midbrain organoids, leading us to finally select BAG956. Furthermore, BAG956 significantly reverses characteristic PD phenotypes in α-syn preformed fibril models in vitro and in vivo by promoting autophagic clearance of pathological α-syn aggregates. Following the FDA Modernization Act 2.0's emphasis on alternative non-animal testing methods, our OASIS can serve as an animal-free preclinical test model (newly termed "nonclinical test") for the synucleinopathy drug development.
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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.