ArticleCell reports2019
Impairment of Macroautophagy in Dopamine Neurons Has Opposing Effects on Parkinsonian Pathology and Behavior.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Rapamycin and Autophagy: Potential Therapeutic Approach for Parkinson's Disease Treatment.CNS & neurological disorders drug targets · 2026Review
- Autophagy and Neuropsychiatric Disorders: Unraveling Molecular Mechanisms and Signaling Pathways.CNS & neurological disorders drug targets · 2026Review
- Clearance Pathways for α-Synuclein in Parkinson's Disease.Journal of neurochemistry · 2025Review
- Modulation of autophagy by melatonin and its receptors: implications in brain disorders.Acta pharmacologica Sinica · 2025Review
- Regulation of α-synuclein homeostasis and inflammasome activation by microglial autophagy.Science advances · 2022Review
- Activation of Autophagy Ameliorates Age-Related Neurogenesis Decline and Neurodysfunction in Adult Mice.Stem cell reviews and reports · 2022Article
- The Emerging Roles of Autophagy in Human Diseases.Biomedicines · 2021Review
- Focus on the Small GTPase Rab1: A Key Player in the Pathogenesis of Parkinson's Disease.International journal of molecular sciences · 2021Review
- Targeting autophagy using small-molecule compounds to improve potential therapy of Parkinson's disease.Acta pharmaceutica Sinica. B · 2021Review
- Alpha-Synuclein defects autophagy by impairing SNAP29-mediated autophagosome-lysosome fusion.Cell death & disease · 2021Article
- Genes Implicated in Familial Parkinson's Disease Provide a Dual Picture of Nigral Dopaminergic Neurodegeneration with Mitochondria Taking Center Stage.International journal of molecular sciences · 2021Review
- REST Protects Dopaminergic Neurons from Mitochondrial and α-Synuclein Oligomer Pathology in an Alpha Synuclein Overexpressing BAC-Transgenic Mouse Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Targeting of Lysosomal Pathway Genes for Parkinson's Disease Modification: Insights From Cellular and Animal Models.Frontiers in neurology · 2021Review
- Multifactoriality of Parkinson's Disease as Explored Through Human Neural Stem Cells and Their Transplantation in Middle-Aged Parkinsonian Mice.Frontiers in pharmacology · 2021Article
- Melatonin and Autophagy in Aging-Related Neurodegenerative Diseases.International journal of molecular sciences · 2020Review
- NaSH increases SIRT1 activity and autophagy flux through sulfhydration to protect SH-SY5Y cells induced by MPP~.Cell cycle (Georgetown, Tex.) · 2020Article
- Autophagy in Parkinson's Disease.Journal of molecular biology · 2020Review
- Assessing Autophagy in Archived Tissue or How to Capture Autophagic Flux from a Tissue Snapshot.Biology · 2020Article
- Autophagy-Based Hypothesis on the Role of Brain Catecholamine Response During Stress.Frontiers in psychiatry · 2020Review
- Autophagy and Redox Homeostasis in Parkinson's: A Crucial Balancing Act.Oxidative medicine and cellular longevity · 2020Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Parkinson's disease (PD) is characterized by the death of dopamine neurons in the substantia nigra pars compacta (SNc) and accumulation of α-synuclein. Impaired autophagy has been implicated and activation of autophagy proposed as a treatment strategy. We generate a human α-synuclein-expressing mouse model of PD with macroautophagic failure in dopamine neurons to understand the interaction between impaired macroautophagy and α-synuclein. We find that impaired macroautophagy generates p62-positive inclusions and progressive neuron loss in the SNc. Despite this parkinsonian pathology, motor phenotypes accompanying human α-synuclein overexpression actually improve with impaired macroautophagy. Real-time fast-scan cyclic voltammetry reveals that macroautophagy impairment in dopamine neurons increases evoked extracellular concentrations of dopamine, reduces dopamine uptake, and relieves paired-stimulus depression. Our findings show that impaired macroautophagy paradoxically enhances dopamine neurotransmission, improving movement while worsening pathology, suggesting that changes to dopamine synapse function compensate for and conceal the underlying PD pathogenesis, with implications for therapies that target autophagy.
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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.