Dataset Information

Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis.

ABSTRACT: Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are endogenous lipid mediators that suppress inflammation. Their actions are terminated by the intracellular cysteine amidase, N-acylethanolamine acid amidase (NAAA). Even though NAAA may offer a new target for anti-inflammatory therapy, the lipid-like structures and reactive warheads of current NAAA inhibitors limit the use of these agents as oral drugs. A series of novel benzothiazole-piperazine derivatives that inhibit NAAA in a potent and selective manner by a non-covalent mechanism are described. A prototype member of this class (8) displays high oral bioavailability, access to the central nervous system (CNS), and strong activity in a mouse model of multiple sclerosis (MS). This compound exemplifies a second generation of non-covalent NAAA inhibitors that may be useful in the treatment of MS and other chronic CNS disorders.

SUBMITTER: Migliore M

PROVIDER: S-EPMC5009002 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis.

Migliore Marco M Pontis Silvia S Fuentes de Arriba Angel Luis AL Realini Natalia N Torrente Esther E Armirotti Andrea A Romeo Elisa E Di Martino Simona S Russo Debora D Pizzirani Daniela D Summa Maria M Lanfranco Massimiliano M Ottonello Giuliana G Busquet Perrine P Jung Kwang-Mook KM Garcia-Guzman Miguel M Heim Roger R Scarpelli Rita R Piomelli Daniele D

Angewandte Chemie (International ed. in English) 20160712 37

Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are endogenous lipid mediators that suppress inflammation. Their actions are terminated by the intracellular cysteine amidase, N-acylethanolamine acid amidase (NAAA). Even though NAAA may offer a new target for anti-inflammatory therapy, the lipid-like structures and reactive warheads of current NAAA inhibitors limit the use of these agents as oral drugs. A series of novel benzothiazole-piperazine derivatives that inhibit NAAA in a potent ...[more]

PMID: 27404798

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Project description:BACKGROUND:There are inconsistent reports about multiple sclerosis (MS) risk among migrants from low to high MS risk geographical regions. This study assessed the overall MS incidence and evaluated seasonality in birth and subsequent MS risk later in the life in second generation of migrants born and lived in Kuwait. METHODS:We assessed the overall and gender-specific MS risk in second generation of migrants born and lived in Kuwait between January 1, 1950 and April 30, 2013. Data on migrants' MS patients diagnosed and registered in Kuwait National MS Registry were used. Hewitt's non-parametric test was carried out to evaluate the seasonality in migrants' MS births in comparison with the second generation migrants' births in general population. RESULTS:During the study period, an overall risk of migrants' MS births (per 100,000 non-Kuwaiti births in general population) was 23.8 (95% CI: 20.8 - 27.0). Gender-specific MS risk showed that non-Kuwaiti female had statistically significant (p?=?0.003) higher risk (28.6; 95% CI: 24.2 - 33.7) than non-Kuwaiti males (18.7; 95% CI: 15.1-23.0). The month-specific distribution of migrants' MS births compared with migrants' births in general population did not differ significantly (?2 goodness-of-fit test statistic?=?9.51, p?=?0.575). Hewitt's non-parametric test revealed an evidence of slight but statistically non-significant (p?=?0.090) increased tendency of migrants' MS births during September through February. CONCLUSIONS:The proportion of migrants' MS births (per 100,000 migrants' births in general population) over the study period was 23.8 (95% CI: 20.8 - 27.0), which was statistically significantly higher than the previously reported Kuwaiti national MS births (16.2; 95% CI: 15.1-17.4) in Kuwait. Non-parametric analysis showed slight but statistically non-significant increased tendency of migrants' MS births from September through February. Knowledge of MS risk factors and how and when they act among genetically vulnerable individuals from gestation to early adulthood will help design prevention strategies.

Dataset Information

Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis.

Publications

Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis.

Similar Datasets

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