ELIZA

return kwic search for effect out of >500 occurrences
566982 occurrences (No.17 in the rank) during 5 years in the PubMed. [cache]

370) Firstly, we phenotypically screened a library of 31 small molecules using a cellular model of necroptosis and, thereafter, the hit compound effect was validated in vivo in a sub-acute 1-methyl-1-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) PD-related mouse model.

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PMID:34069782 DOI:10.3390/ijms22105289

2021 International journal of molecular sciences

* Discovery of a Necroptosis Inhibitor Improving Dopaminergic Neuronal Loss after MPTP Exposure in Mice.

- Parkinson's disease (PD) is the second most common neurodegenerative disorder, mainly characterized by motor deficits correlated with progressive dopaminergic neuronal loss in the substantia nigra pars compacta (SN). Necroptosis is a caspase-independent form of regulated cell death mediated by the concerted action of receptor-interacting protein 3 (RIP3) and the pseudokinase mixed lineage domain-like protein (MLKL). It is also usually dependent on RIP1 kinase activity, influenced by further cellular clues. Importantly, necroptosis appears to be strongly linked to several neurodegenerative diseases, including PD. Here, we aimed at identifying novel chemical inhibitors of necroptosis in a PD-mimicking model, by conducting a two-step screening. Firstly, we phenotypically screened a library of 31 small molecules using a cellular model of necroptosis and, thereafter, the hit compound effect was validated in vivo in a sub-acute 1-methyl-1-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) PD-related mouse model. From the initial compounds, we identified one hit-Oxa12-that strongly inhibited necroptosis induced by the pan-caspase inhibitor zVAD-fmk in the BV2 murine microglia cell line. More importantly, mice exposed to MPTP and further treated with Oxa12 showed protection against MPTP-induced dopaminergic neuronal loss in the SN and striatum. In conclusion, we identified Oxa12 as a hit compound that represents a new chemotype to tackle necroptosis. Oxa12 displays in vivo effects, making this compound a drug candidate for further optimization to attenuate PD pathogenesis.

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(1)219 of	(8)11 sizes	(15)3 to	(22)2 measure
(2)66 on	(9)9 is	(16)3 via	(23)2 relationship
(3)30 null	(10)4 against	(17)3 with	(24)2 than
(4)20 and	(11)4 for	(18)2 P	(25)2 trials
(5)19 in	(12)4 such	(19)2 at
(6)16 was	(13)4 that	(20)2 estimates,
(7)13 size	(14)3 may	(21)2 induced

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--- WordNet output for effect --- =>趣旨, 結果, 影響, 効力, 活動, 印象, 効果, 成し遂げる Overview of noun effect The noun effect has 6 senses (first 5 from tagged texts) 1. (101) consequence, effect, outcome, result, event, issue, upshot -- (a phenomenon that follows and is caused by some previous phenomenon; "the magnetic effect was greater when the rod was lengthwise"; "his decision had depressing consequences for business"; "he acted very wise after the event") 2. (11) impression, effect -- (an outward appearance; "he made a good impression"; "I wanted to create an impression of success"; "she retained that bold effect in her reproductions of the original painting") 3. (9) effect -- (an impression (especially one that is artificial or contrived); "he just did it for effect") 4. (2) effect, essence, burden, core, gist -- (the central meaning or theme of a speech or literary work) 5. (1) effect, force -- ((of a law) having legal validity; "the law is still in effect") 6. effect -- (a symptom caused by an illness or a drug; "the effects of sleep loss"; "the effect of the anesthetic") Overview of verb effect The verb effect has 2 senses (first 2 from tagged texts) 1. (17) effect, effectuate, set up -- (produce; "The scientists set up a shock wave") 2. (3) effect -- (act so as to bring into existence; "effect a change") --- WordNet end ---