ArticleAutophagy2022
LGALS3 (galectin 3) mediates an unconventional secretion of SNCA/α-synuclein in response to lysosomal membrane damage by the autophagic-lysosomal pathway in human midbrain dopamine neurons.
Article in Autophagy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 67 citations in OpenAlex.
- α-Synuclein blocks endoplasmic reticulum co-translational protein translocation early in Parkinson's disease.Nature communications · 2026Article
- Modeling Parkinson's pathology in human iPSC dopaminergic neurons uncovers key mechanisms of Lewy body formation and heterogeneity.Science advances · 2026Article
- Evaluation of a human 3D multi-spheroid model derived from SH-SY5Y cells for cytotoxicity testing.Scientific reports · 2026Article
- Ginsenoside Rg1 alleviates post-ischemic stroke neuroinflammation by inhibiting CKLF1-mediated suppression of dead/dying neuron clearance.Acta pharmaceutica Sinica. B · 2026Article
- The emerging role and therapeutic targeting of autophagy-lysosome pathway in the pathogenesis of Parkinson's disease.Translational neurodegeneration · 2026Review
- Galectin-3 as a Key Driver of Neuroinflammation and α-Synuclein Aggregation in Parkinson's Disease: Unlocking New Paths for Biomarkers and Therapies.Cell biochemistry and biophysics · 2026Review
- Intravenous immunoglobulin remodels innate immune cell communication and induces differential autophagy pathways in Kawasaki disease.Frontiers in immunology · 2026Article
- TRIM16: a context-dependent E3 ligase in autophagy, oxidative stress, and immune regulation - from cancer and systemic disease.Frontiers in oncology · 2026Review
- Internalized SNCA/α-synuclein fibrils become truncated and resist degradation in neurons while glial cells rapidly degrade SNCA fibrils.Autophagy · 2026Article
- Impairment of lysosomal quality control in Huntington disease.Cell death & disease · 2025Article
- Pleiotropic regulatory mechanisms and targeted therapeutic prospects of Galectin-3 in aging-related diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- CKLF1 disrupts microglial efferocytosis following acute ischemic stroke by binding to phosphatidylserine.Cell death and differentiation · 2025Article
- Role of Cellular Senescence in Parkinson's Disease: Potential for Disease-Modification Through Senotherapy.Biomedicines · 2025Review
- Endocytic tethers modulate unconventional GAPDH secretion.Cell surface (Amsterdam, Netherlands) · 2025Article
- Neuronal constitutive endolysosomal perforations enable α-synuclein aggregation by internalized PFFs.The Journal of cell biology · 2025Article
- Exploring the multilayered response of TB bacterium Mycobacterial tuberculosis to lysosomal injury.FEMS microbiology reviews · 2025Review
- The role of autophagy in synucleinopathy: clearance versus spread of α-synuclein.Autophagy reports · 2025Review
- Plekhg5 controls the unconventional secretion of Sod1 by presynaptic secretory autophagy.Nature communications · 2024Article
- Association Between Serum Galectin-3 and Parkinson's Disease: A Two-Sample Mendelian Randomization Study.Brain and behavior · 2024Article
- Lysosome quality control in health and neurodegenerative diseases.Cellular & molecular biology letters · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Numerous lines of evidence support the premise that the misfolding and subsequent accumulation of SNCA/α-synuclein (synuclein alpha) is responsible for the underlying neuronal pathology observed in Parkinson disease (PD) and other synucleinopathies. Moreover, the cell-to-cell transfer of these misfolded SNCA species is thought to be responsible for disease progression and the spread of cellular pathology throughout the brain. Previous work has shown that when exogenous, misfolded SNCA fibrils enter cells through endocytosis, they can damage and rupture the membranes of their endocytotic vesicles in which they are trafficked. Rupture of these vesicular membranes exposes intralumenal glycans leading to galectin protein binding, subsequent autophagic protein recruitment, and, ultimately, their introduction into the autophagic-lysosomal pathway. Increasing evidence indicates that both pathological and non-pathological SNCA species undergo autophagy-dependent unconventional secretion. While other proteins have also been shown to be secreted from cells by autophagy, what triggers this release process and how these specific proteins are recruited to a secretory autophagic pathway is largely unknown. Here, we use a human midbrain dopamine (mDA) neuronal culture model to provide evidence in support of a cellular mechanism that explains the cell-to-cell transfer of pathological forms of SNCA that are observed in PD. We demonstrate that LGALS3 (galectin 3) mediates the release of SNCA following vesicular damage. SNCA release is also dependent on TRIM16 (tripartite motif containing 16) and ATG16L1 (autophagy related 16 like 1), providing evidence that secretion of SNCA is mediated by an autophagic secretory pathway.
Indexed as
Identifiers
What OpenQuestion holds
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.