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| 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 | 糖尿病患者白内障术后脉络膜厚度和黄斑厚度的变化(英文)显示文摘目的:评估糖尿病和非糖尿病患者白内障超声乳化术后脉络膜厚度(SFCT)和黄斑厚度(CMT)的变化。方法:前瞻性研究。包括53例轻度或中度非增殖性糖尿病视网膜病变(NPDR)无黄斑水肿患者和53例行白内障超声乳化术非糖尿病患者。术前、术后1mo和3mo用 EDI-OCT 测量脉络膜厚度和黄斑厚度,并比较两组的SFCT和CMT变化。结果:糖尿病患者中,基线处CMT为267±32 μm。术后CMT显著升高,术后1mo为291±77 μm( P =0.034),术后3mo为293±75 μm( P =0.047)。基线处SFCT为199± 72 μm 。术后SFCT显著升高,术后1mo为231±73 μm ( P = 0.035),术后3mo为248±91 μm( P =0.026)。在非糖尿病患者中,基线处CMT为264±29 μm。术后显著CMT升高,术后1mo为278±42 μm( P <0.001),术后3mo为 276± 56 μm( P =0.028)。基线处SFCT为236±60 μm。术后SFCT显著提高,术后1mo为265±64 μm( P <0.001),术后3mo为240±60 μm( P =0.234)。两组间CMT的变化无统计学差异(均 P >0.05)。尽管非糖尿病组患者的基线脉络膜较厚,但研究组术后1mo( P =0.97)和术后3mo( P =0.97)的SFCT变化无显著差异。结论:术后两组间CMT和SFCT均显著提高。CMT和SFCT变化在糖尿病和非糖尿病患者间无显著不同。 | Saeed Karimi Mohammad Alizadeh Seyed Aliasghar Mosavi Farinaz Borna | 2019 | 国际眼科杂志2019，19，6： | 3 |
| 3 | Prostacyclin is an autocrinere gulator in the contraction of oviductal smooth muscle显示文摘 | Farinaz A Jennifer G Nena M A | 2002 | Hu Reproduc2002，17，12： | 1 |
| 4 | Worst and best-case coverage in sensor networks显示文摘 | Farinaz K and Miodrag P | 2005 | IEEE Transactions on Mobile Computing2005，4，1： | 1 |
| 5 | Expo- sure in Wireless Sensor Networks: Theory and Practical Solu- tions显示文摘 | SEAPAHN MEGERIAN FARINAZ KOUSHANFAR GANG QU GIACOMINO VELTRI MIODRAG POTKONJAK | 2002 | Wireless Networks2002，，8： | 1 |
| 6 | A primer on hardware security : models, methods, and metrics 显示文摘 | Masoud Rostami Farinaz Koushanfar Ramesh Karri | 2014 | Proceedings of the IEEE2014，102，8： | 1 |
| 7 | A survey of hardware trojan taxonomy and detection显示文摘 | Mohammad Tehranipoor Farinaz Koushanfar | 2010 | IEEE design & test of computers2010，27，1： | 1 |
| 8 | Prostacyclin is an autocrine regulator in the contraction of oviductal smooth muscle显示文摘 | Farinaz Arbab Jennifer Goldsby Nena Matijevic-Aleksic | 2002 | Human Reproduction2002，17，12： | 1 |
| 9 | Apelin-13 Protects the Brain A- gainst Ischemic Reperfusion Injury and Cerebral Edema in a Transient Model of Focal Cerebral Ischemia显示文摘 | Mehdi K Nahid A Farinaz N | 2012 | Mol Neurosci2012，，48： | 1 |
| 10 | A Survey of Hardware Trojan Taxonomy and Detection显示文摘 | Mohammad Tehranipoor Farinaz Koushanfar | | 0，，01： | 1 |
| 11 | Role of serine proteases in inflammation: Bowman–Birk protease inhibitor (BBI) as a potential therapy for autoimmune diseases显示文摘 | Farinaz Safavi Abdolmohamad Rostami | 2012 | Experimental and Molecular Pathology2012，，3： | 1 |
| 12 | Exposure in Wireless Sensor Networks: Theory and Practical Solutions显示文摘 | Seapahn Megerian Farinaz Koushanfar Gang Qu Giacomino Veltri Miodrag Potkonjak | 2002 | Wireless Networks2002，，5： | 1 |
| 13 | A Survey of hardware Trojan taxonomy and detection 显示文摘 | Mohammad T Farinaz K | 2010 | IEEE Design And Test of Computers2010，，1： | 1 |
| 14 | Exposure in wireless sensor networks: theory and practical solutions显示文摘 | Seapahn Megerian Farinaz Koushanfar Gang Qu | 2002 | Wireless Networks2002，8，： | 1 |
| 15 | Worst and best-case coverage in sensor networks显示文摘 | Seapahn Megerian Farinaz Koushanfar Miodrag Pot- konjak | 2005 | IEEE Transactions on Mobile Computing2005，4，1： | 1 |
| 16 | Implications of Warm mix Asphalt on Long-term Oxidative Ageing and Fatigue Performance of Asphalt Binders and Mixtures 显示文摘 | FARINAZ S JONG-SUB L LUIS A H DN | 2014 | Road Materials and Pave- ment Design2014，15，1： | 1 |
| 17 | Impact of Nursing Intervention on Improving HIV, Hepatitis Knowledge and Mental Health Among Homeless Young Adults显示文摘 | Adeline Nyamathi Barbara Kennedy Catherine Branson Benissa Salem Farinaz Khalilifard Mary Marfisee Daniel Getzoff Barbara Leake | 2013 | Community Mental Health Journal2013，，2： | 1 |
| 18 | Coverage Problems in Wireless Ad Hoc Sensor Networks显示文摘 | K Farinaz P Miodrag | 2001 | INFOCOM''012001，，3： | 1 |
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