daisybell
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This is from Medscape - I thought it was interesting, but am not sure how relevant findings like this are for us!
An international, interdisciplinary group of researchers, centered at the Clinical Institute of Neurology in Vienna, has demonstrated how Parkinson disease can spread from cell to cell in the human brain.[1] They accomplished this by using an antibody developed in collaboration with a German biotech firm; it is the first to distinguish between the normal and the disease-associated forms of alpha-synuclein. With the antibody the researchers found that human nerve cells take a pathologic alpha-synuclein and transfer the disease from one cell to the next in a process akin to an infection. The investigators observed that such a mechanism of spread from cell to cell can serve as a point of therapeutic intervention by blocking the transfer mechanism. In a related study,[2] they also showed that the new antibody can be used to detect disease-associated alpha-synuclein in the cerebrospinal fluid of patients with synucleinopathies, allowing for early diagnosis of dementias owing to parkinsonian-related diseases.
Intracellular processing of disease-associated α-synuclein in the human brain suggests prion-like cell-to-cell spread.
Neurobiol Dis. 2014; 69:76-92 (ISSN: 1095-953X)
Kovacs GG; Breydo L; Green R; Kis V; Puska G; Lőrincz P; Perju-Dumbrava L; Giera R; Pirker W; Lutz M; Lachmann I; Budka H; Uversky VN; Molnár K; László L
Dementia with Lewy bodies (DLB), Parkinson's disease (PD) and multiple system atrophy are characterized by the deposition of disease-associated α-synuclein. In the present study we 1) examined the molecular specificity of the novel anti-α-synuclein 5G4 antibody; 2) evaluated immunoreactivity patterns and their correlation in human brain tissue with micro- and astrogliosis in 57 cases with PD or DLB; and 3) performed a systematic immunoelectron microscopical mapping of subcellular localizations. 5G4 strongly binds to the high molecular weight fraction of β-sheet rich oligomers, while no binding to primarily disordered oligomers or monomers was observed. We show novel localizations of disease-associated α-synuclein including perivascular macrophages, ependyma and cranial nerves. α-Synuclein immunoreactive neuropil dots and thin threads associate more with glial reaction than Lewy bodies alone. Astrocytic α-synuclein is an important component of the pathology. Furthermore, we document ultrastructurally the pathway of processing of disease-associated α-synuclein within neurons and astroglial cells. Interaction of mitochondria and disease-associated α-synuclein plays a key role in the molecular-structural cytopathogenesis of disorders with Lewy bodies. We conclude that 1) the 5G4 antibody has strong selectivity for β-sheet rich α-synuclein oligomers; 2) Lewy bodies themselves are not the most relevant morphological substrate that evokes tissue lesioning; 3) both neurons and astrocytes internalize disease-associated α-synuclein in the human brain, suggesting prion-like cell-to-cell spread of α-synuclein by uptake from surrounding structures, as shown previously in experimental observations.
An international, interdisciplinary group of researchers, centered at the Clinical Institute of Neurology in Vienna, has demonstrated how Parkinson disease can spread from cell to cell in the human brain.[1] They accomplished this by using an antibody developed in collaboration with a German biotech firm; it is the first to distinguish between the normal and the disease-associated forms of alpha-synuclein. With the antibody the researchers found that human nerve cells take a pathologic alpha-synuclein and transfer the disease from one cell to the next in a process akin to an infection. The investigators observed that such a mechanism of spread from cell to cell can serve as a point of therapeutic intervention by blocking the transfer mechanism. In a related study,[2] they also showed that the new antibody can be used to detect disease-associated alpha-synuclein in the cerebrospinal fluid of patients with synucleinopathies, allowing for early diagnosis of dementias owing to parkinsonian-related diseases.
Intracellular processing of disease-associated α-synuclein in the human brain suggests prion-like cell-to-cell spread.
Neurobiol Dis. 2014; 69:76-92 (ISSN: 1095-953X)
Kovacs GG; Breydo L; Green R; Kis V; Puska G; Lőrincz P; Perju-Dumbrava L; Giera R; Pirker W; Lutz M; Lachmann I; Budka H; Uversky VN; Molnár K; László L
Dementia with Lewy bodies (DLB), Parkinson's disease (PD) and multiple system atrophy are characterized by the deposition of disease-associated α-synuclein. In the present study we 1) examined the molecular specificity of the novel anti-α-synuclein 5G4 antibody; 2) evaluated immunoreactivity patterns and their correlation in human brain tissue with micro- and astrogliosis in 57 cases with PD or DLB; and 3) performed a systematic immunoelectron microscopical mapping of subcellular localizations. 5G4 strongly binds to the high molecular weight fraction of β-sheet rich oligomers, while no binding to primarily disordered oligomers or monomers was observed. We show novel localizations of disease-associated α-synuclein including perivascular macrophages, ependyma and cranial nerves. α-Synuclein immunoreactive neuropil dots and thin threads associate more with glial reaction than Lewy bodies alone. Astrocytic α-synuclein is an important component of the pathology. Furthermore, we document ultrastructurally the pathway of processing of disease-associated α-synuclein within neurons and astroglial cells. Interaction of mitochondria and disease-associated α-synuclein plays a key role in the molecular-structural cytopathogenesis of disorders with Lewy bodies. We conclude that 1) the 5G4 antibody has strong selectivity for β-sheet rich α-synuclein oligomers; 2) Lewy bodies themselves are not the most relevant morphological substrate that evokes tissue lesioning; 3) both neurons and astrocytes internalize disease-associated α-synuclein in the human brain, suggesting prion-like cell-to-cell spread of α-synuclein by uptake from surrounding structures, as shown previously in experimental observations.