ArticleActa neuropathologica communications2021
Accumulation of alpha-synuclein within the liver, potential role in the clearance of brain pathology associated with Parkinson's disease.
Article in Acta neuropathologica communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 54 citations in OpenAlex.
- Cerebrospinal fluid and dural accumulation of α-synuclein impairs CNS clearance in Parkinson's disease.The Journal of experimental medicine · 2026Article
- Identification of divergent organ-specific gene and protein expression signatures for mitochondrial function, inflammatory response, and proteostasis in the liver and brain in the rotenone-induced rat model of Parkinson's disease.Molecular biology reports · 2026Article
- Blood-Based α-Synuclein Biomarkers in Parkinson's Disease: Molecular Diversity, Analytical Advances and Clinical Translation.International journal of molecular sciences · 2026Review
- Parkinson's disease: pathogenesis and therapeutic strategies.Molecular biomedicine · 2026Review
- Ultra-performance liquid chromatography-mass spectrometry analysis of post-mortem brain tissue reveals specific amino acid profile dysregulation in Parkinson's disease and Alzheimer's disease patients.NPJ Parkinson's disease · 2026Article
- Proteome-scale autoantibody profiling in PSC: Associations with clinical phenotypes and evidence for neuroendocrine deregulations.JHEP reports : innovation in hepatology · 2026Article
- Beyond the Brain: Exploring the multi-organ axes in Parkinson's disease pathogenesis.Journal of advanced research · 2026Review
- Biological aging predicts mortality in Parkinson's patients: evidence from UK Biobank.NPJ Parkinson's disease · 2026Article
- Beyond Organ Boundaries: Molecular Mechanisms of Hepatic Encephalopathy and Parkinson's Disease from the Perspective of the Gut-Liver-Brain Axis.Research (Washington, D.C.) · 2026Review
- Dairy-rich diet triggers hepatic α-synuclein pathology via the liver-brain axis in GBA1-related Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Neurodegeneration as Ecosystem Failure: A New Paradigm for Prevention and Treatment.International journal of molecular sciences · 2025Review
- Hepatic function is associated with cognitive function in patients with stable schizophrenia.BMC psychiatry · 2025Article
- Inherited Genetic Variation in Parkinson's Disease: Convergence on Impaired Autophagosome-Lysosome Fusion Through the Altered Expression of mRNA Isoforms.Molecular neurobiology · 2025Article
- Alpha-synuclein interacts with regulators of ATP homeostasis in mitochondria.Nature communications · 2025Article
- Bridging systemic metabolic dysfunction and Alzheimer's disease: the liver interface.Molecular neurodegeneration · 2025Review
- Autonomic dysfunction in neurodegenerative disease.Nature reviews. Neuroscience · 2025Review
- Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances.Signal transduction and targeted therapy · 2025Review
- Propagation of pathologic α-synuclein from kidney to brain may contribute to Parkinson's disease.Nature neuroscience · 2025Article
- From blood vessels to brain cells: Connecting the circulatory system and Parkinson's disease.Journal of Parkinson's disease · 2025Review
- Peripheral proteinopathy in neurodegenerative diseases.Translational neurodegeneration · 2025Review
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alpha-synuclein (α-syn) aggregation is the hallmark pathological lesion in brains of patients with Parkinson's disease (PD) and related neurological disorders characterized as synucleinopathies. Accumulating evidence now indicates that α-syn deposition is also present within the gut and other peripheral organs outside the central nervous system (CNS). In the current study, we demonstrate for the first time that α-syn pathology also accumulates within the liver, the main organ responsible for substance clearance and detoxification. We further demonstrate that cultured human hepatocytes readily internalize oligomeric α-syn assemblies mediated, at least in part, by the gap junction protein connexin-32 (Cx32). Moreover, we identified a time-dependent accumulation of α-syn within the liver of three different transgenic (tg) mouse models expressing human α-syn under CNS-specific promoters, despite the lack of α-syn mRNA expression within the liver. Such a brain-to-liver transmission route could be further corroborated by detection of α-syn pathology within the liver of wild type mice one month after a single striatal α-syn injection. In contrast to the synucleinopathy models, aged mice modeling AD rarely show any amyloid-beta (Aß) deposition within the liver. In human post-mortem liver tissue, we identified cases with neuropathologically confirmed α-syn pathology containing α-syn within hepatocellular structures to a higher degree (75%) than control subjects without α-syn accumulation in the brain (57%). Our results reveal that α-syn accumulates within the liver and may be derived from the brain or other peripheral sources. Collectively, our findings indicate that the liver may play a role in the clearance and detoxification of pathological proteins in PD and related synucleinopathies.
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