Matches in SemOpenAlex for { <https://semopenalex.org/work/W4318707435> ?p ?o ?g. }
- W4318707435 abstract "Abstract Synucleinopathies form a group of neurodegenerative diseases defined by misfolding and aggregation of alpha-synuclein (α-syn). Abnormal accumulation and spreading of α-syn aggregates lead to synapse dysfunction and neuronal cell death. Yet, little is known about synaptic mechanisms underlying α-syn pathology. Here we identified β-isoforms of neurexins (β-NRXs) as presynaptic organizing proteins that interact with α-syn preformed fibrils (α-syn PFFs), toxic α-syn aggregates, but not α-syn monomers. Our cell surface protein binding assays and surface plasmon resonance assays reveal that α-syn PFFs bind directly to β-NRX through their N-terminal histidine-rich domain (HRD) at nanomolar range (Kd: ~500 nM monomer equivalent). Furthermore, our artificial synapse formation assays show that α-syn PFFs diminish excitatory and inhibitory presynaptic organization induced by a specific isoform of neuroligin 1 that binds only β-NRXs, but not α-isoforms of neurexins. Thus, our data suggest that α-syn PFFs interact with β-NRXs to inhibit β-NRX-mediated presynaptic organization, providing novel molecular insight into how α-syn PFFs induce synaptic pathology in synucleinopathies such as Parkinson’s disease and dementia with Lewy bodies." @default.
- W4318707435 created "2023-02-01" @default.
- W4318707435 creator A5013297849 @default.
- W4318707435 creator A5015351067 @default.
- W4318707435 creator A5019228061 @default.
- W4318707435 creator A5033720368 @default.
- W4318707435 creator A5045303406 @default.
- W4318707435 creator A5050509115 @default.
- W4318707435 creator A5055526256 @default.
- W4318707435 creator A5062212424 @default.
- W4318707435 creator A5063176241 @default.
- W4318707435 creator A5064921244 @default.
- W4318707435 date "2023-01-30" @default.
- W4318707435 modified "2023-10-03" @default.
- W4318707435 title "α-synuclein preformed fibrils bind to β-neurexins and impair β-neurexin-mediated presynaptic organization" @default.
- W4318707435 cites W1512936397 @default.
- W4318707435 cites W1527671059 @default.
- W4318707435 cites W1553785885 @default.
- W4318707435 cites W1625129845 @default.
- W4318707435 cites W1965095016 @default.
- W4318707435 cites W1969244755 @default.
- W4318707435 cites W1976118830 @default.
- W4318707435 cites W1988011192 @default.
- W4318707435 cites W1989913002 @default.
- W4318707435 cites W1990122129 @default.
- W4318707435 cites W1991154017 @default.
- W4318707435 cites W1992257474 @default.
- W4318707435 cites W2014739744 @default.
- W4318707435 cites W2024744542 @default.
- W4318707435 cites W2029978572 @default.
- W4318707435 cites W2037543187 @default.
- W4318707435 cites W2037948191 @default.
- W4318707435 cites W2046165746 @default.
- W4318707435 cites W2050465941 @default.
- W4318707435 cites W2050647292 @default.
- W4318707435 cites W2058474765 @default.
- W4318707435 cites W2061463538 @default.
- W4318707435 cites W2066155243 @default.
- W4318707435 cites W2069261633 @default.
- W4318707435 cites W2069486808 @default.
- W4318707435 cites W2072147769 @default.
- W4318707435 cites W2072878433 @default.
- W4318707435 cites W2074369549 @default.
- W4318707435 cites W2091396384 @default.
- W4318707435 cites W2098730433 @default.
- W4318707435 cites W2100421640 @default.
- W4318707435 cites W2117503265 @default.
- W4318707435 cites W2120551490 @default.
- W4318707435 cites W2126402425 @default.
- W4318707435 cites W2131710583 @default.
- W4318707435 cites W2136203517 @default.
- W4318707435 cites W2145331523 @default.
- W4318707435 cites W2146526204 @default.
- W4318707435 cites W2152889422 @default.
- W4318707435 cites W2153536347 @default.
- W4318707435 cites W2154450864 @default.
- W4318707435 cites W2157320870 @default.
- W4318707435 cites W2158524945 @default.
- W4318707435 cites W2158556702 @default.
- W4318707435 cites W2162687166 @default.
- W4318707435 cites W2162690000 @default.
- W4318707435 cites W2171526610 @default.
- W4318707435 cites W2308756493 @default.
- W4318707435 cites W2325022883 @default.
- W4318707435 cites W2507718676 @default.
- W4318707435 cites W2523905541 @default.
- W4318707435 cites W2587082207 @default.
- W4318707435 cites W2587921648 @default.
- W4318707435 cites W2591352502 @default.
- W4318707435 cites W2608948341 @default.
- W4318707435 cites W2749938990 @default.
- W4318707435 cites W2758608092 @default.
- W4318707435 cites W2765792294 @default.
- W4318707435 cites W2768863537 @default.
- W4318707435 cites W2771190354 @default.
- W4318707435 cites W2781489829 @default.
- W4318707435 cites W2801024124 @default.
- W4318707435 cites W2868639160 @default.
- W4318707435 cites W2890022816 @default.
- W4318707435 cites W2943550823 @default.
- W4318707435 cites W2953534538 @default.
- W4318707435 cites W2955413884 @default.
- W4318707435 cites W3003788831 @default.
- W4318707435 cites W3011755495 @default.
- W4318707435 cites W3082757515 @default.
- W4318707435 cites W3092037660 @default.
- W4318707435 cites W3100786721 @default.
- W4318707435 cites W3167236756 @default.
- W4318707435 cites W4206989713 @default.
- W4318707435 cites W4220987338 @default.
- W4318707435 cites W4223942559 @default.
- W4318707435 cites W4235774781 @default.
- W4318707435 cites W4299426269 @default.
- W4318707435 cites W4318039932 @default.
- W4318707435 cites W4361960923 @default.
- W4318707435 doi "https://doi.org/10.1101/2023.01.28.526024" @default.
- W4318707435 hasPublicationYear "2023" @default.
- W4318707435 type Work @default.
- W4318707435 citedByCount "1" @default.
- W4318707435 countsByYear W43187074352023 @default.