Bacterial DNA induces the formation of heat-resistant disease-associated “Tetz-proteins” in human plasma

Tetz, Victor; Tetz, George

doi:10.1101/604090

Cited by 1 publication

(1 citation statement)

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“…Extracellular bacterial DNA induces prion aggregation within microbial biofilm matrices and plays the critical role of converting bacterial amyloid into highly ordered, aggregated cross-β structures enabling unique structural properties of microbial biofilms [31,32]. A recent report identified the association between bacterial extracellular DNA and the formation of heat-resistant protein fractions within different proteins – even those lacking prion domains [33]. We hypothesize that DNA can act as an efficient promoter for protein misfolding in AD pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Bacterial DNA promotes Tau aggregation

Tetz¹,

Pinho²,

Soto³

et al. 2019

Preprint

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A hallmark feature of Alzheimer’s disease (AD) and other tauopathies is the misfolding, aggregation and cerebral accumulation of tau deposits. Compelling evidence indicates that misfolded tau aggregates are neurotoxic, producing synaptic loss and neuronal damage. Misfolded tau aggregates are able to spread the pathology from cell-to-cell by a prion like seeding mechanism. The factors implicated in the initiation and progression of tau misfolding and aggregation are largely unclear. In this study, we evaluated the effect of DNA extracted from diverse prokaryotic and eukaryotic cells in tau misfolding and aggregation. Our results show that DNA from various, unrelated gram-positive and gram-negative bacteria results in a more pronounced tau misfolding compared to eukaryotic DNA. Interestingly, a higher effect in promoting tau aggregation was observed for DNA extracted from certain bacterial species previously detected in the brain, CSF or oral cavity of patients with AD. Our findings indicate that microbial DNA may play a previously overlooked role in the propagation of tau protein misfolding and AD pathogenesis, providing a new conceptual framework that positions the compromised blood-brain and intestinal barriers as important sources of microbial DNA in the CNS, opening novel opportunities for therapeutic interventions.

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Section: Introductionmentioning

confidence: 99%