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	题名	作者	年代	出处	被引量
1	Vitamin B12 modulates Parkinson’s disease LRRK2 kinase activity through allosteric regulation and confers neuroprotection显示文摘Missense mutations in Leucine-Rich Repeat Kinase 2(LRRK2)cause the majority of familial and some sporadic forms of Parkinson’s disease(PD).The hyperactivity of LRRK2 kinase induced by the pathogenic mutations underlies neurotoxicity,promoting the development of LRRK2 kinase inhibitors as therapeutics.Many potent and specific small-molecule LRRK2 inhibitors have been reported with promise.However,nearly all inhibitors are ATP competitive—some with unwanted side effects and unclear clinical outcome—alternative types of LRRK2 inhibitors are lacking.Herein we identify 5′-deoxyadenosylcobalamin(AdoCbl),a physiological form of the essential micronutrient vitamin B12 as a mixed-type allosteric inhibitor of LRRK2 kinase activity.Multiple assays show that AdoCbl directly binds LRRK2,leading to the alterations of protein conformation and ATP binding in LRRK2.STD-NMR analysis of a LRRK2 homologous kinase reveals the contact sites in AdoCbl that interface with the kinase domain.Furthermore,we provide evidence that AdoCbl modulates LRRK2 activity through disrupting LRRK2 dimerization.Treatment with AdoCbl inhibits LRRK2 kinase activity in cultured cells and brain tissue,and prevents neurotoxicity in cultured primary rodent neurons as well as in transgenic C.elegans and D.melanogaster expressing LRRK2 disease variants.Finally,AdoCbl alleviates deficits in dopamine release sustainability caused by LRRK2 disease variants in mouse models.Our study uncovers vitamin B12 as a novel class of LRRK2 kinase modulator with a distinct mechanism,which can be harnessed to develop new LRRK2-based PD therapeutics in the future.	Adam Schaffner Xianting Li Yacob Gomez-Llorente Emmanouela Leandrou Anna Memou Nicolina Clemente Chen Yao Farinaz Afsari Lianteng Zhi Nina Pan Keita Morohashi Xiaoluan Hua Ming-Ming Zhou Chunyu Wang Hui Zhang Shu G.Chen Christopher J.Elliott Hardy Rideout Iban Ubarretxena-Belandia Zhenyu Yue	2019	Cell Research2019，29，4：	7
2	Clamp-Assisted Reduction of High Subtrochanteric Fractures of the Fe- mur显示文摘	Alan Afsari Frank Liporance Eric Lind- vail	2010	JBJS2010，92，：	1
3	The anterior intra-pelvic (modified rives-stoppa) approach for fixation of acetabular frac- tures显示文摘	SAGI HC AFSARI A DZIADOSZ D	2010	Journal of Orthopaedic Trauma2010，24，5：	1
4	The anterior intra-pelvic (modified rives stoppa) approach for fixation of acetabular fractures显示文摘	Sagi HC Afsari A Dziadosz D		0，，05：	1
5	The anterior intra-pelvic ( modified Rives-Stoppa) approach for fixation of acetabular fractures显示文摘	Sagi HC Afsari A Dziadosz D	2010	J Or- thop Trauma2010，24，5：	1
6	The anterior intra-pelvic (modified rives-stoppa) approach for fixation of acetabular fractures显示文摘	Sagi HC Afsari A Dziadosz D	2010	J Orthop Trauma2010，24，5：	1
7	The anteri- or intra - pelvic ( modified rives - stoppa ) approach for fixation of acetabular fractures 显示文摘	Sagi HC Afsari A Dziadosz D	2010	J Orthop Trauma2010，24，5：	1
8	The anterior intra-pelvic(modified rives stoppa)approach for fixation of acetabular fractures显示文摘	Sagi HC Afsari A Dziadosz D	2010	J Orthop Trauma2010，24，5：	1
9	The anterior intra-pelvic (modified rives-stoppa) approach for fixation of acetabular fractures显示文摘	Sagi HC Afsari A Dziadosz D		0，，05：	1
10	Prevalence of anisometropia and its association with refractive error and amblyopia in preschool children显示文摘	Afsari S Rose KA Gole GA	2013	Br J Ophthalmol2013，97，9：	1
11	A simple and reproducible breast cancer prognostic test显示文摘	Marchionni L Afsari B Geman D	2013	BMC Genomics2013，14，1：	1
12	The effect of proges- terone suppositories on threatened abortion: a randomized clinical trial 显示文摘	Yassaee F Shekarriz-Foumani R Afsari S	2014	J Reprod Infertil2014，15，3：	1
13	The anterior intra-pelvic(modified rives-stoppa)approach for fixation of acetabular fractures显示文摘	Sagi HC Afsari A Dziadosz D	2010	J Orthop Trauma2010，24，5：	1
14	The anterior intra-pelvic(modified rives-stoppa) approachfor fixation of acetabular fractures显示文摘	Sagi HC Afsari A Dziadosz D	2010	J Orthop trauma2010，24，5：	1
15	The anterior intra-pelvic (modified rives-stoppa) approach for fixation of acetabular fractures显示文摘	Sagi HC Afsari A Dziadosz D	2010	J Orthop Trauma2010，24，5：	1
16	The anterior intra-pelvic (modified rives-stoppa) approach for fixation of acetabular fi'actures 显示文摘	$agi HC Afsari A Dziadosz D	2010	J Or- thop Trauma2010，24，5：	1
17	The anterior intraztaelvic (modi- fied rives-Stoppa) approach for fixation of acetabular fractures 显示文摘	Sagi HC Afsari A Dziadosz D	2010	J Orthop Trauma2010，24，5：	1
18	Multiparameter analysis of human bone marrow stromal cells identifies distinct immu- nomodulatory and differentiation-competent subtypes显示文摘	JAMES S FOX J AFSARI F	2015	Stem Cell Reports2015，4，6：	1
19	The anterior intra - pelvic (modified rives- stoppa) approach for fixation of acetabular fractures 显示文摘	Sagi HC Afsari A Dziadosz D	2010	J Orthop Trau- ma2010，24，5：	1
20	Outcome analysis of pancreaticoduodenectomy at a community hospital显示文摘	Afsari A Zhandoug Z Young S	2002	Am Surg2002，68，3：	1

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