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LRRK2 functions as a scaffolding kinase of ASK1-mediated neuronal cell death
Yoon, J.H.,Mo, J.S.,Kim, M.Y.,Ann, E.J.,Ahn, J.S.,Jo, E.H.,Lee, H.J.,Lee, Y.C.,Seol, W.,Yarmoluk, S.M.,Gasser, T.,Kahle, P.J.,Liu, G.H.,Belmonte, J.C.I.,Park, H.S. Elsevier Biomedical Press 2017 Biochimica et biophysica acta, Molecular cell rese Vol.1864 No.12
Leucine-rich repeat kinase 2 (LRRK2), a multi-domain protein, is a key causative factor in Parkinson's disease (PD). Identification of novel substrates and the molecular mechanisms underlying the effects of LRRK2 are essential for understanding the pathogenesis of PD. In this study, we showed that LRRK2 played an important role in neuronal cell death by directly phosphorylating and activating apoptosis signal-regulating kinase 1 (ASK1). LRRK2 phosphorylated ASK1 at Thr832 that is adjacent to Thr845, which serves as an autophosphorylation site. Moreover, results of binding and kinase assays showed that LRRK2 acted as a scaffolding protein by interacting with each components of the ASK1-MKK3/6-p38 MAPK pathway through its specific domains and increasing the proximity to downstream targets. Furthermore, LRRK2-induced apoptosis was suppressed by ASK1 inhibition in neuronal stem cells derived from patients with PD. These results clearly indicate that LRRK2 acts as an upstream kinase in the ASK1 pathway and plays an important role in the pathogenesis of PD.
마렉백신의 In-Ovo 접종에 따른 육계에서의 효능 평가
엄현정,원미영,이동우,고도욱,모인필,Um, H.J.,Won, M.Y.,Lee, D.W.,Go, D.W.,Mo, I.P. 한국가금학회 2006 韓國家禽學會誌 Vol.33 No.4
본 실험은 육계에서의 Marek's disease(MD) 백신에 대한 안전성과 효용성을 국내에 기 도입된 18일령 계란에서의 백신 접종 방법(In-Ovo vaccination)을 이용하여 평가하고자 실시하였다. 육계에서의 MD 오염율은 nested PCR을 이용하였으며 백신 접종군과 비접종군간의 생산성 차이를 출하 일령, 평균출하체중, 출하율, 사료 효율을 기본으로 하는 생산 지수를 측정하여 비교하였다. 백신에 의한 면역 억제 현상을 파악하기 위하여 접종 농장에서 채취한 혈청에서의 항체 역가수준과 F낭의 무게 변화를 검사하였다. 국내 육계에서의 MD 발생율을 파악하기 위하여 nested PCR을 실시한 결과 조사 대상 농장 중 26.09%가 오염되었으며, 백신 접종 농장과 비접종 농장간의 생산 지수의 차이는 통계학적으로 유의한 차이가 없었다. 그러나 MDV 오염군에서의 MD 백신 접종 농장의 생산 지수가 비접종 농장보다 높아 간접적으로 효과가 있음이 인정되었다. 면역 억제여부를 파악하기 위한 검사에서는 두 그룹 간 B/B ratio 차이는 없었으나 두 계군 모두 출하 시 심한 위축을 보여주어 혈청 검사 성적과 연계하여 볼 때 국내 육계 농장에서의 IBD 감염이 만연되어 있다는 것을 알 수 있었다. 본 연구를 통해서 국내 육계에서의 MDV 오염율이 파악되었으며, In-Ovo 백신 접종에 의한 MD 백신 접종은 안전성에 있어서는 별다른 문제가 없었으나 효능면에 있어서는 MD 야외감염율이 낮고 IBD와 같은 면역 억제 질병의 감염이 만연되어 있어 정확한 평가가 되지 않아 앞으로 후속 연구가 진행되어야 할 것으로 판단되었다. This study has been designed to evaluate the efficacy of MD in-ovo vaccination in broiler and to find the contamination level of MD virus in broiler farms. A nested PCR test was used to find the level of filed contamination of pathogenic MD virus in the commercial broiler farms. The positive rate of farms contaminated with pathogenic MD virus was 26.09%. And to evaluate the efficacy of MD vaccination, performance factors such as the mortality, feed conversion rate and body weight at market age has been recorded and compared among farms. There was no difference on these factors between vaccinated and non-vaccinated farms except performance. We need further investigation of the film with low performance index. The B/B ratio, which is common index for the evaluation of bursal changes, was calculated and compared between vaccinated and non-vaccinated group There were significant decreases of B/B ratio in the both group without any statistical difference between groups. The reason of decreased bursal size may be due to other infection such as IBD. From this study, we can know that the contamination rate of fm with pathogenic MD virus was very low and not different from previous study. However, the difference of the contamination rate in different locations recommends periodical monitoring on these areas.