Alpha synuclein PFFs seed the formation of new fibrils from a pool of active monomers, inducing Lewy body pathology in neurons.
New tau PFFs cause tau monomers to aggregate into neurofibrillary tangles, leading to the tau pathology seen in Alzheimer’s Disease.
Induce Lewy body pathology in vitro and in vivo by seeding fibrillation of alpha synuclein monomers
Immunocytochemistry/immunofluorescence analysis of Sprague-Dawley rat primary hippocampal neurons treated with Type 1 human alpha synuclein PFFs (left) and Type 1 mouse alpha synuclein PFFs (right). Neurons treated with the fibrils show Lewy body inclusion formation.
Immunohistochemistry analysis of Sprague-Dawley rat brain injected with Type 1 mouse alpha synuclein PFFs. 30 days post-injection. Alpha synuclein pathology is seen in the periform/insular cortex and the cingulate cortex on both the same (ipsi) and opposite (contra) sides as the injection sites.
Left: TEM of Type 1 human preformed fibrils. Right: TEM of Type 2 human preformed fibrils. Fibrils were sonicated and treated with uranyl acetate.
Thioflavin T emission curve (left) shows increased fluorescence (correlated to alpha synuclein protein fibrillation) when Type 1 PFFs are combined with monomers. TEM of Type 1 mouse alpha synuclein preformed fibrils (right). Magnification: 100kx.
Tau preformed fibrils (PFFs) (left). Thioflavin T emission curve (right) shows increased fluorescence (correlated to tau protein fibrillization) when tau PFFs are combined with tau monomers. Tau PFFs induce tau aggregation in cultured cells by recruiting soluble monomers into insoluble fibrils and tangles.
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