J. M. Thomas

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA study of cation environment and movement during dehydration and reduction of nickel-exchanged zeolite Y by x-ray absorption and diffractionE. Dooryhee, C. R. A. Catlow, J. W. Couves, P. J. Maddox, J. M. Thomas, G. N. Greaves, A. T. Steel, and R. P. TownsendCite this: J. Phys. Chem. 1991, 95, 11, 4514–4521Publication Date (Print):May 1, 1991Publication History Published online1 May 2002Published inissue 1 May 1991https://pubs.acs.org/doi/10.1021/j100164a062https://doi.org/10.1021/j100164a062research-articleACS PublicationsRequest reuse permissionsArticle Views397Altmetric-Citations91LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts

Mutations in the leucine-rich repeat kinase-2 (LRRK2) gene cause autosomal-dominant Parkinson's disease (PD) and contribute to sporadic PD. LRRK2 contains Guanosine-5'-triphosphate (GTP) binding, GTPase and kinase activities that have been implicated in the neuronal degeneration of PD pathogenesis, making LRRK2, a potential drug target. To date, there is no disease-modifying drug to slow the neuronal degeneration of PD and no published LRRK2 GTP domain inhibitor. Here, the biological functions of two novel GTP-binding inhibitors of LRRK2 were examined in PD cell and mouse models. Through a combination of computer-aided drug design (CADD) and LRRK2 bio-functional screens, two novel compounds, 68: and 70: , were shown to reduce LRRK2 GTP binding and to inhibit LRRK2 kinase activity in vitro and in cultured cell assays. Moreover, these two compounds attenuated neuronal degeneration in human SH-SY5Y neuroblastoma cells and mouse primary neurons expressing mutant LRRK2 variants. Although both compounds inhibited LRRK2 kinase activity and reduced neuronal degeneration, solubility problems with 70: prevented further testing in mice. Thus, only 68: was tested in a LRRK2-based lipopolysaccharide (LPS)-induced pre-inflammatory mouse model. 68: reduced LRRK2 GTP-binding activity and kinase activity in brains of LRRK2 transgenic mice after intraperitoneal injection. Moreover, LPS induced LRRK2 upregulation and microglia activation in mouse brains. These findings suggest that disruption of GTP binding to LRRK2 represents a potential novel therapeutic approach for PD intervention and that these novel GTP-binding inhibitors provide both tools and lead compounds for future drug development.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInterfacial electron-transfer reactions between platinum colloids and reducing radicals in aqueous solutionA. Harriman, G. R. Millward, P. Neta, M. C. Richoux, and J. M. ThomasCite this: J. Phys. Chem. 1988, 92, 5, 1286–1290Publication Date (Print):March 1, 1988Publication History Published online1 May 2002Published inissue 1 March 1988https://pubs.acs.org/doi/10.1021/j100316a054https://doi.org/10.1021/j100316a054research-articleACS PublicationsRequest reuse permissionsArticle Views749Altmetric-Citations68LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts

Overall rate constants for the removal of N2(A,v) by O2 and O were measured at 298 K in a rapidly pumped flow reactor using laser-induced fluorescence (LIF) detection of N2(A,v) by excitation in the first positive system of N2, B(3πg)←A(3Σ+u). O atoms were generated in microwave discharges of pure O2 prepared by thermal decomposition of KMnO4. Measured rate constants for N2(A,v)+O2 increased from 2.5×10−12(v=0) to 5.7×10−12 cm3 s−1(v=3). For N2(A,v)+O(3P), they were an order of magnitude larger, rising from 3.5×10−11(v=(0) to 5.2×10−11 cm3 s−1(v=3). They are compared with previous work and discussed in terms of the likely molecular interaction that they represent.