FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4225308889> ?p ?o ?g. }

• W4225308889 abstract "α-synuclein (α-Syn) is intimately linked to synucleinopathies like Parkinson's disease and dementia with Lewy bodies. However, the pathophysiological mechanisms that are triggered by this protein are still largely enigmatic. α-Syn overabundance may cause neurodegeneration through protein accumulation and mitochondrial deterioration but may also result in pathomechanisms independent from neuronal cell death. One such proposed pathological mechanism is the influence of α-Syn on non-stimulated, intrinsic brain activity. This activity is responsible for more than 90% of the brain's energyconsumption, and is thus thought to play an eminent role in basic brain functionality. Here we report that α-Syn substantially disrupts intrinsic neuronal network burst activity in a long-term neuronal cell culture model. Mechanistically, the impairment of network activity originates from reduced levels of cyclic AMP and cyclic AMP-mediated signaling as well as from diminished numbers of active presynaptic terminals. The profound reduction of network activity due to α-Syn was mediated only by intracellularly expressed α-Syn, but not by α-Syn that is naturally released by neurons. Conversely, extracellular pre-formed fibrils of α-Syn mimicked the effect of intracellular α-Syn, suggesting that they trigger an off-target mechanism that is not activated by naturally released α-Syn. A simulation-based model of the network activity in our cultures demonstrated that even subtle effect sizes in reducing outbound connectivity, i.e., loss of active synapses, can cause substantial global reductions in non-stimulated network activity. These results suggest that even low-level loss of synaptic output capabilities caused by α-Syn may result in significant functional impairments in terms of intrinsic neuronal network activity. Provided that our model holds true for the human brain, then α-Syn may cause significant functional lesions independent from neurodegeneration." @default.
• W4225308889 created "2022-05-05" @default.
• W4225308889 creator A5016418059 @default.
• W4225308889 creator A5017530320 @default.
• W4225308889 creator A5050072898 @default.
• W4225308889 creator A5064832285 @default.
• W4225308889 creator A5069984125 @default.
• W4225308889 creator A5079452617 @default.
• W4225308889 creator A5081431133 @default.
• W4225308889 date "2022-05-03" @default.
• W4225308889 modified "2023-10-02" @default.
• W4225308889 title "α-Synuclein Impacts on Intrinsic Neuronal Network Activity Through Reduced Levels of Cyclic AMP and Diminished Numbers of Active Presynaptic Terminals" @default.
• W4225308889 cites W1586971759 @default.
• W4225308889 cites W1770278075 @default.
• W4225308889 cites W1965095016 @default.
• W4225308889 cites W1966409098 @default.
• W4225308889 cites W1974861764 @default.
• W4225308889 cites W1977761644 @default.
• W4225308889 cites W1985811626 @default.
• W4225308889 cites W1992343776 @default.
• W4225308889 cites W2002677234 @default.
• W4225308889 cites W2004092055 @default.
• W4225308889 cites W2009573330 @default.
• W4225308889 cites W2014531915 @default.
• W4225308889 cites W2015701831 @default.
• W4225308889 cites W2022664336 @default.
• W4225308889 cites W2022671987 @default.
• W4225308889 cites W2044879928 @default.
• W4225308889 cites W2045044466 @default.
• W4225308889 cites W2046166566 @default.
• W4225308889 cites W2057447099 @default.
• W4225308889 cites W2063057031 @default.
• W4225308889 cites W2065236536 @default.
• W4225308889 cites W2070093918 @default.
• W4225308889 cites W2075793841 @default.
• W4225308889 cites W2088642285 @default.
• W4225308889 cites W2089900719 @default.
• W4225308889 cites W2090281903 @default.
• W4225308889 cites W2091537996 @default.
• W4225308889 cites W2105392557 @default.
• W4225308889 cites W2108060249 @default.
• W4225308889 cites W2114327504 @default.
• W4225308889 cites W2123358805 @default.
• W4225308889 cites W2127389037 @default.
• W4225308889 cites W2128212150 @default.
• W4225308889 cites W2128631317 @default.
• W4225308889 cites W2130050860 @default.
• W4225308889 cites W2136882542 @default.
• W4225308889 cites W2147461093 @default.
• W4225308889 cites W2147546041 @default.
• W4225308889 cites W2151479669 @default.
• W4225308889 cites W2164285935 @default.
• W4225308889 cites W2164406367 @default.
• W4225308889 cites W2164653071 @default.
• W4225308889 cites W2166555967 @default.
• W4225308889 cites W2280506293 @default.
• W4225308889 cites W2310305711 @default.
• W4225308889 cites W2324392087 @default.
• W4225308889 cites W2337829485 @default.
• W4225308889 cites W2417670847 @default.
• W4225308889 cites W2423726595 @default.
• W4225308889 cites W2588578683 @default.
• W4225308889 cites W2594349582 @default.
• W4225308889 cites W2596287310 @default.
• W4225308889 cites W2596953817 @default.
• W4225308889 cites W2612979254 @default.
• W4225308889 cites W2621775373 @default.
• W4225308889 cites W2765650007 @default.
• W4225308889 cites W2787177558 @default.
• W4225308889 cites W2790799100 @default.
• W4225308889 cites W2791797416 @default.
• W4225308889 cites W2794054536 @default.
• W4225308889 cites W2803487190 @default.
• W4225308889 cites W2807040929 @default.
• W4225308889 cites W2909581763 @default.
• W4225308889 cites W2914576615 @default.
• W4225308889 cites W2924664474 @default.
• W4225308889 cites W2945702369 @default.
• W4225308889 cites W2947275333 @default.
• W4225308889 cites W2956449351 @default.
• W4225308889 cites W2964889816 @default.
• W4225308889 cites W2974009117 @default.
• W4225308889 cites W2991267786 @default.
• W4225308889 cites W2999229807 @default.
• W4225308889 cites W3004801161 @default.
• W4225308889 cites W3039696582 @default.
• W4225308889 cites W3085460930 @default.
• W4225308889 cites W3092016236 @default.
• W4225308889 cites W3104752958 @default.
• W4225308889 cites W3128017238 @default.
• W4225308889 doi "https://doi.org/10.3389/fnmol.2022.868790" @default.
• W4225308889 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35721317" @default.
• W4225308889 hasPublicationYear "2022" @default.
• W4225308889 type Work @default.
• W4225308889 citedByCount "1" @default.
• W4225308889 countsByYear W42253088892023 @default.
• W4225308889 crossrefType "journal-article" @default.
• W4225308889 hasAuthorship W4225308889A5016418059 @default.
• W4225308889 hasAuthorship W4225308889A5017530320 @default.
• W4225308889 hasAuthorship W4225308889A5050072898 @default.

• next