ArticleActa neuropathologica2023
Urinary tract infections trigger synucleinopathy via the innate immune response.
Article in Acta neuropathologica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 22 citations in OpenAlex.
- Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Therapeutic effects of Icariside II on radiation cystitis: revealing the mechanistic role of the FN1/Itgαvβ6-PI3K/AKT signaling pathway using single-cell RNA sequencing.International journal of surgery (London, England) · 2026Article
- Single-nucleus brain transcriptomics reveals microglia dysfunction in multiple system atrophy.Nature communications · 2026Article
- Harnessing pro-inflammatory and immunopathologic immune responses in urinary tract infections for vaccine development: it's all about a balance.Frontiers in immunology · 2026Review
- Multiple system atrophy: advances in pathogenesis and emerging therapeutic strategies.Journal of neurology · 2025Review
- Propagation of pathologic α-synuclein from kidney to brain may contribute to Parkinson's disease.Nature neuroscience · 2025Article
- Lewy body diseases and the gut.Molecular neurodegeneration · 2025Review
- Review
- Variants in Lrrk2 and Snca deficiency do not alter the course of primary encephalitis due to neurotropic reovirus T3D in newborn mice.PloS one · 2025Article
- Autoantibody profiles in Alzheimer´s, Parkinson´s, and dementia with Lewy bodies: altered IgG affinity and IgG/IgM/IgA responses to alpha-synuclein, amyloid-beta, and tau in disease-specific pathological patterns.Journal of neuroinflammation · 2024Article
- Chronic urinary tract infections cause persistent microglial changes in a humanized ɑ-synuclein mouse model.Journal of Parkinson's disease · 2024Article
- Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis.Movement disorders : official journal of the Movement Disorder Society · 2024Review
- Current insights and assumptions on α-synuclein in Lewy body disease.Acta neuropathologica · 2024Review
- Assessing serum anti-nuclear antibodies HEp-2 patterns in synucleinopathies.Immunity & ageing : I & A · 2024Article
- Infections in the Etiology of Parkinson's Disease and Synucleinopathies: A Renewed Perspective, Mechanistic Insights, and Therapeutic Implications.Journal of Parkinson's disease · 2024Review
- Probing the diagnostic values of plasma cf-nDNA and cf-mtDNA for Parkinson's disease and multiple system atrophy.Frontiers in neuroscience · 2024Article
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Authors and funding
27 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Symptoms in the urogenital organs are common in multiple system atrophy (MSA), also in the years preceding the MSA diagnosis. It is unknown how MSA is triggered and these observations in prodromal MSA led us to hypothesize that synucleinopathy could be triggered by infection of the genitourinary tract causing ɑ-synuclein (ɑSyn) to aggregate in peripheral nerves innervating these organs. As a first proof that peripheral infections could act as a trigger in MSA, this study focused on lower urinary tract infections (UTIs), given the relevance and high frequency of UTIs in prodromal MSA, although other types of infection might also be important triggers of MSA. We performed an epidemiological nested-case control study in the Danish population showing that UTIs are associated with future diagnosis of MSA several years after infection and that it impacts risk in both men and women. Bacterial infection of the urinary bladder triggers synucleinopathy in mice and we propose a novel role of ɑSyn in the innate immune system response to bacteria. Urinary tract infection with uropathogenic E. coli results in the de novo aggregation of ɑSyn during neutrophil infiltration. During the infection, ɑSyn is released extracellularly from neutrophils as part of their extracellular traps. Injection of MSA aggregates into the urinary bladder leads to motor deficits and propagation of ɑSyn pathology to the central nervous system in mice overexpressing oligodendroglial ɑSyn. Repeated UTIs lead to progressive development of synucleinopathy with oligodendroglial involvement in vivo. Our results link bacterial infections with synucleinopathy and show that a host response to environmental triggers can result in ɑSyn pathology that bears semblance to MSA.
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