ArticleNature communications2024
Disruption of lysosomal proteolysis in astrocytes facilitates midbrain organoid proteostasis failure in an early-onset Parkinson's disease model.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Current potential biomarkers for Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis: review of literature.Dialogues in clinical neuroscience · 2026Review
- Organoids: Key advances, optimization, and technological iterations in their application to neurodegenerative diseases.Neural regeneration research · 2026Article
- Astrocytes in Neurodegeneration: Spatial States, Crosstalk, and Emerging Therapies.Molecular neurobiology · 2026Review
- Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates.Acta pharmaceutica Sinica. B · 2026Review
- Astrocytes orchestrate neuroprotection and pathogenesis via bidirectional neuronal interactions in Parkinson's disease.Journal of physiology and biochemistry · 2026Review
- Research progress of traditional Chinese medicine interventions for aging-related nervous system diseases.Biogerontology · 2026Review
- The vicious cycle: unraveling the interplay between α-synuclein, mitochondrial dysfunction, and neuroinflammation in Parkinson's disease.Journal of neurology · 2026Review
- ATP13A2 Loss of Function-Driven Polyamine Dysregulation Induces SAM Depletion and Epigenetic Astrocyte Toxicity.bioRxiv : the preprint server for biology · 2026Article
- Article
- Autophagy dysfunction in iPSCs-derived neurons and midbrain organoids carrying a SNCA triplication.NPJ Parkinson's disease · 2026Article
- Review
- Single-cell transcriptomics revealed molecular vulnerability in a human midbrain-like organoid model of Parkinson's disease.iScience · 2026Article
- Cycloastragenol Derivatives Improve Tyrosine Metabolism, Regulate TLR4/NF-κB/TERT Signaling Pathways, and Inhibit MPTP Induced Neuroinflammation and PD Symptoms.CNS neuroscience & therapeutics · 2026Article
- Special characteristics of human astrocytes and their roles in brain homeostasis.Neuroscience applied · 2026Review
- Astrocytes in Parkinson's Disease: From Guardians to Accomplices.Clinical interventions in aging · 2026Review
- Ketogenic diet and Parkinson's disease.Frontiers in molecular neuroscience · 2026Review
- Organoids in Cancer Research and Regenerative Medicine: Current Status, Challenges, and Future Prospects.MedComm · 2026Review
- Review
- Investigation of CNS damage following HIV infection and methamphetamine exposure using human iPSC-derived microglia and 3D cerebral assembloid models.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Accumulation of advanced glycation end products (AGEs) on biopolymers accompanies cellular aging and drives poorly understood disease processes. Here, we studied how AGEs contribute to development of early onset Parkinson's Disease (PD) caused by loss-of-function of DJ1, a protein deglycase. In induced pluripotent stem cell (iPSC)-derived midbrain organoid models deficient for DJ1 activity, we find that lysosomal proteolysis is impaired, causing AGEs to accumulate, α-synuclein (α-syn) phosphorylation to increase, and proteins to aggregate. We demonstrated these processes are at least partly driven by astrocytes, as DJ1 loss reduces their capacity to provide metabolic support and triggers acquisition of a pro-inflammatory phenotype. Consistently, in co-cultures, we find that DJ1-expressing astrocytes are able to reverse the proteolysis deficits of DJ1 knockout midbrain neurons. In conclusion, astrocytes' capacity to clear toxic damaged proteins is critical to preserve neuronal function and their dysfunction contributes to the neurodegeneration observed in a DJ1 loss-of-function PD model.
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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.