ArticleThe Journal of biological chemistry2019
Autophagy activation promotes clearance of α-synuclein inclusions in fibril-seeded human neural cells.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 116 citations in OpenAlex.
- Neuron-derived extracellular vesicles to examine brain mTOR target engagement with sirolimus in patients with multiple system atrophy.Parkinsonism & related disorders · 2023Trial
- mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double-Blind, Placebo-Controlled Futility Trial and 1-Year Biomarker Longitudinal Analysis.Movement disorders : official journal of the Movement Disorder Society · 2022Trial
- Lipid metabolism dysregulation in Parkinson's disease: A Mendelian randomization and transcriptomic analysis.IBRO neuroscience reports · 2026Article
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- Modeling Parkinson's pathology in human iPSC dopaminergic neurons uncovers key mechanisms of Lewy body formation and heterogeneity.Science advances · 2026Article
- Copper Overload Affects α-Synuclein Clearance Mechanisms in a Parkinson's Disease In Vitro Model.Advanced biology · 2026Article
- The α-synuclein proteostasis network and its translational applications in Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Phloretin as a Multitarget Neuroprotective Agent: Mechanistic Insights into the Modulation of Oxidative Stress, Inflammation, and Apoptosis.Neuromolecular medicine · 2026Review
- Breaking the proteasome balance: α-synuclein and the ubiquitin-proteasome system.Frontiers in cell and developmental biology · 2026Review
- Treatment ofFrontiers in toxicology · 2026Article
- Modulation of O-GlcNAc cycling influences α-synuclein amplification, degradation, and associated neuroinflammatory pathology.Molecular neurodegeneration · 2025Article
- Recent Advances in Autophagy and Immunotherapy for the Clearance of Aggregated α-Synuclein in Parkinson's Disease.Aging and disease · 2025Review
- Dopamine and cortical neurons with different Parkinsonian mutations show variation in lysosomal and mitochondrial dysfunction.NPJ Parkinson's disease · 2025Article
- Epicoccin A Ameliorates PD-like Symptoms in Zebrafish: Enhancement of PINK1/Parkin-Dependent Mitophagy and Inhibition of Excessive Oxidative Stress.Marine drugs · 2025Article
- Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health.The Journal of cell biology · 2025Review
- Canonical and noncanonical autophagy: involvement in Parkinson's disease.Frontiers in cell and developmental biology · 2025Review
- Neuromodulation influences T lymphocyte calcium signaling and alpha synuclein clearance: implications for Parkinson's disease.Frontiers in cellular neuroscience · 2025Review
- The role of autophagy in synucleinopathy: clearance versus spread of α-synuclein.Autophagy reports · 2025Review
- α-Synuclein pathology as a target in neurodegenerative diseases.Nature reviews. Neurology · 2025Review
- Astrocytes contribute to toll-like receptor 2-mediated neurodegeneration and alpha-synuclein pathology in a human midbrain Parkinson's model.Translational neurodegeneration · 2024Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There is much interest in delineating the mechanisms by which the α-synuclein protein accumulates in brains of individuals with Parkinson's disease (PD). Preclinical studies with rodent and primate models have indicated that fibrillar forms of α-synuclein can initiate the propagation of endogenous α-synuclein pathology. However, the underlying mechanisms by which α-synuclein fibrils seed pathology remain unclear. To investigate this further, we have used exogenous fibrillar α-synuclein to seed endogenous α-synuclein pathology in human neuronal cell lines, including primary human neurons differentiated from induced pluripotent stem cells. Fluorescence microscopy and immunoblot analyses were used to monitor levels of α-synuclein and key autophagy/lysosomal proteins over time in the exogenous α-synuclein fibril-treated neurons. We observed that temporal changes in the accumulation of cytoplasmic α-synuclein inclusions were associated with changes in the key autophagy/lysosomal markers. Of note, chloroquine-mediated blockade of autophagy increased accumulation of α-synuclein inclusions, and rapamycin-induced activation of autophagy, or use of 5'-AMP-activated protein kinase (AMPK) agonists, promoted the clearance of fibril-mediated α-synuclein pathology. These results suggest a key role for autophagy in clearing fibrillar α-synuclein pathologies in human neuronal cells. We propose that our findings may help inform the development of human neural cell models for screening of potential therapeutic compounds for PD or for providing insight into the mechanisms of α-synuclein propagation. Our results further add to existing evidence that AMPK activation may be a therapeutic option for managing PD.
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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.