+検索条件
-Structure paper
タイトル | Vaccination with structurally adapted fungal protein fibrils induces immunity to Parkinson's disease. |
---|---|
ジャーナル・号・ページ | Brain, Vol. 147, Issue 5, Page 1644-1652, Year 2024 |
掲載日 | 2024年5月3日 |
著者 | Verena Pesch / José Miguel Flores-Fernandez / Sara Reithofer / Liang Ma / Pelin Özdüzenciler / Yannick Busch / Aishwarya Sriraman / YongLiang Wang / Sara Amidian / Chiara V M Kroepel / Laura Müller / Yi Lien / Olivia Rudtke / Benedikt Frieg / Gunnar F Schröder / Holger Wille / Gültekin Tamgüney / |
PubMed 要旨 | The pathological misfolding and aggregation of soluble α-synuclein into toxic oligomers and insoluble amyloid fibrils causes Parkinson's disease, a progressive age-related neurodegenerative disease ...The pathological misfolding and aggregation of soluble α-synuclein into toxic oligomers and insoluble amyloid fibrils causes Parkinson's disease, a progressive age-related neurodegenerative disease for which there is no cure. HET-s is a soluble fungal protein that can form assembled amyloid fibrils in its prion state. We engineered HET-s(218-298) to form four different fibrillar vaccine candidates, each displaying a specific conformational epitope present on the surface of α-synuclein fibrils. Vaccination with these four vaccine candidates prolonged the survival of immunized TgM83+/- mice challenged with α-synuclein fibrils by 8% when injected into the brain to model brain-first Parkinson's disease or by 21% and 22% when injected into the peritoneum or gut wall, respectively, to model body-first Parkinson's disease. Antibodies from fully immunized mice recognized α-synuclein fibrils and brain homogenates from patients with Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Conformation-specific vaccines that mimic epitopes present only on the surface of pathological fibrils but not on soluble monomers, hold great promise for protection against Parkinson's disease, related synucleinopathies and other amyloidogenic protein misfolding disorders. |
リンク | Brain / PubMed:38428032 / PubMed Central |
手法 | EM (らせん対称) |
解像度 | 3.1 Å |
構造データ | EMDB-17111, PDB-8oqi: |
由来 |
|
キーワード | PROTEIN FIBRIL / alpha-synuclein / amyloid / fibril / Parkinson's disease |