ArticleHuman molecular genetics2020
Synj1 haploinsufficiency causes dopamine neuron vulnerability and alpha-synuclein accumulation in mice.
Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 49 citations in OpenAlex.
- Roles of autophagy in brain homeostasis and disease.Nature neuroscience · 2026Review
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Synaptojanin1 regulates synaptic dopamine release and axonal integrity via retromer-dependent endosomal sorting.Research square · 2026Article
- Strategies for Optimizing Genetic Mouse Models to Enhance the Understanding of Parkinson's Disease.Biomedicines · 2026Review
- The emerging role and therapeutic targeting of autophagy-lysosome pathway in the pathogenesis of Parkinson's disease.Translational neurodegeneration · 2026Review
- New insights into synaptic vesicle dysfunction in Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Roles in physiology and disease of the inositol phosphatase synaptojanin 1.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026Review
- In vivo Proximity & Spatial Proteomics with CRISPR Screening Identify STXBP1 as a Protective Modifier of α-synuclein Toxicity in Dopamine Neurons.bioRxiv : the preprint server for biology · 2026Article
- Accurate and robust 3D genome feature discovery from multiplexed DNA FISH.bioRxiv : the preprint server for biology · 2025Article
- A phosphoinositide switch from PI(4,5)PScience advances · 2025Article
- Synaptojanin-1 supports VPS35-dependent trafficking of dopamine D2 autoreceptors at presynaptic terminals.Research square · 2025Article
- Haploinsufficiency of ITSN1 is associated with a substantial increased risk of Parkinson's disease.Cell reports · 2025Article
- Spermidine Recovers the Autophagy Defects Underlying the Pathophysiology of Cell Trafficking Disorders.Journal of inherited metabolic disease · 2025Article
- Endosomal traffic disorders: a driving force behind neurodegenerative diseases.Translational neurodegeneration · 2024Review
- Lipids associated with autophagy: mechanisms and therapeutic targets.Cell death discovery · 2024Review
- A candidate loss-of-function variant in SGIP1 causes synaptic dysfunction and recessive parkinsonism.Cell reports. Medicine · 2024Article
- Identification of SYNJ1 in a Complex Case of Juvenile Parkinsonism Using a Multiomics Approach.International journal of molecular sciences · 2024Article
- Parkinson's disease gene, Synaptojanin1, dysregulates the surface maintenance of the dopamine transporter.NPJ Parkinson's disease · 2024Article
- Co-occurrence of PRKN and SYNJ1 variants in Early-Onset Parkinson's disease.Metabolic brain disease · 2024Article
- Cell biology of Parkinson's disease: Mechanisms of synaptic, lysosomal, and mitochondrial dysfunction.Current opinion in neurobiology · 2024Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Synaptojanin1 (synj1) is a phosphoinositide phosphatase with dual SAC1 and 5'-phosphatase enzymatic activities in regulating phospholipid signaling. The brain-enriched isoform has been shown to participate in synaptic vesicle (SV) recycling. More recently, recessive human mutations were identified in the two phosphatase domains of SYNJ1, including R258Q, R459P and R839C, which are linked to rare forms of early-onset Parkinsonism. We now demonstrate that Synj1 heterozygous deletion (Synj1+/-), which is associated with an impaired 5'-phosphatase activity, also leads to Parkinson's disease (PD)-like pathologies in mice. We report that male Synj1+/- mice display age-dependent motor function abnormalities as well as alpha-synuclein accumulation, impaired autophagy and dopaminergic terminal degeneration. Synj1+/- mice contain elevated 5'-phosphatase substrate, PI(4,5)P2, particularly in the midbrain neurons. Moreover, pharmacological elevation of membrane PI(4,5)P2 in cultured neurons impairs SV endocytosis, specifically in midbrain neurons, and further exacerbates SV trafficking defects in Synj1+/- midbrain neurons. We demonstrate down-regulation of SYNJ1 transcript in a subset of sporadic PD brains, implicating a potential role of Synj1 deficiency in the decline of dopaminergic function during aging.
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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.