Activation of FADD-Dependent neuronal death pathways as a predictor of pathogenicity for LRRK2 mutations
Συγγραφέας
Melachroinou K., Leandrou E., Valkimadi P.-E., Memou A., Hadjigeorgiou G., Stefanis L., Rideout H.J.Ημερομηνία
2016Γλώσσα
en
Λέξη-κλειδί
Επιτομή
Background Despite the plethora of sequence variants in LRRK2, only a few clearly segregate with PD. Even within this group of pathogenic mutations, the phenotypic profile can differ widely. Objective We examined multiple properties of LRRK2 behavior in cellular models over-expressing three sequence variants described in Greek PD patients in comparison to several known pathogenic and non-pathogenic LRRK2 mutations, to determine if specific phenotypes associated with pathogenic LRRK2 can be observed in other less-common sequence variants for which pathogenicity is unclear based on clinical and/or genetic data alone. Methods The oligomerization, activity, phosphorylation, and interaction with FADD was assessed in HEK293T cells over-expressing LRRK2; while the induction of neuronal death was determined by quantifying apoptotic nuclei in primary neurons transiently expressing LRRK2. Results One LRRK2 variant, A211V, exhibited a modest increase in kinase activity, whereas only the pathogenic mutants G2019S and I2020T displayed significantly altered auto-phosphorylation. We observed an induction of detergent-insoluble high molecular weight structures upon expression of pathogenic LRRK2 mutants, but not the other LRRK2 variants. In contrast, each of the variants tested induced apoptotic death of cultured neurons similar to pathogenic LRRK2 in a FADD-dependent manner. © 2016 Melachroinou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Collections
Related items
Showing items related by title, author, creator and subject.
-
Low-Grade Systemic Inflammation Interferes with Anabolic and Catabolic Characteristics of the Aged Human Skeletal Muscle
Draganidis D., Jamurtas A.Z., Chondrogianni N., Mastorakos G., Jung T., Grune T., Papadopoulos C., Papanikolaou K., Papassotiriou I., Papaevgeniou N., Poulios A., Batrakoulis A., Deli C.K., Georgakouli K., Chatzinikolaou A., Karagounis L.G., Fatouros I.G. (2021)Aging is associated with the development of chronic low-grade systemic inflammation (LGSI) characterized by increased circulating levels of proinflammatory cytokines and acute phase proteins such as C-reactive protein ... -
PD-1 and PD-L1 as immunotherapy targets and biomarkers in non-small cell lung cancer
Tsoukalas N., Kiakou M., Tsapakidis K., Tolia M., Aravantinou-Fatorou E., Baxevanos P., Kyrgias G., Theocharis S. (2019)The integration of immunotherapeutic agents in the treatment of non-small cell lung cancer (NSCLC) has revolutionized the approach of the prevalent type of lung cancer. Although PD-1 and its ligands (PD-L1 and PD-L2) are ... -
Global, regional, and national age-sex specifc mortality for 264 causes of death, 1980-2016: A systematic analysis for the Global Burden of Disease Study 2016
Naghavi M., Abajobir A.A., Abbafati C., Abbas K.M., Abd-Allah F., Abera S.F., Aboyans V., Adetokunboh O., Ärnlöv J., Afshin A., Agrawal A., Kiadaliri A.A., Ahmadi A., Ahmed M.B., Aichour A.N., Aichour I., Aichour M.T.E., Aiyar S., Al-Eyadhy A., Alahdab F., Al-Aly Z., Alam K., Alam N., Alam T., Alene K.A., Ali S.D., Alizadeh-Navaei R., Alkaabi J.M., Alkerwi A., Alla F., Allebeck P., Allen C., Al-Raddadi R., Alsharif U., Altirkawi K.A., Alvis-Guzman N., Amare A.T., Amini E., Ammar W., Amoako Y.A., Anber N., Andersen H.H., Andrei C.L., Androudi S., Ansari H., Antonio C.A.T., Anwari P., Arora M., Artaman A., Aryal K.K., Asayesh H., Asgedom S.W., Atey T.M., Avila-Burgos L., Avokpaho E.F.G.A., Awasthi A., Quintanilla B.P.A., Béjot Y., Babalola T.K., Bacha U., Balakrishnan K., Barac A., Barboza M.A., Barker-Collo S.L., Barquera S., Barregard L., Barrero L.H., Baune B.T., Bedi N., Beghi E., Bekele B.B., Bell M.L., Bennett J.R., Bensenor I.M., Berhane A., Bernabé E., Betsu B.D., Beuran M., Bhatt S., Biadgilign S., Bienhof K., Bikbov B., Bisanzio D., Bourne R.R.A., Breitborde N.J.K., Bulto L.N.B., Bumgarner B.R., Butt Z.A., Cárdenas R., Cahuana-Hurtado L., Cameron E., Campuzano J.C., Car J., Carrero J.J., Carter A., Casey D.C., Castañeda-Orjuela C.A., Catalá-López F., Charlson F.J., Chibueze C.E., Chimed-Ochir O., Chisumpa V.H., Chitheer A.A., Christopher D.J., Ciobanu L.G., Cirillo M., Cohen A.J., Colombara D., Cooper C., Cowie B.C., Criqui M.H., Dandona L., Dandona R., Dargan P.I., Das Neves J., Davitoiu D.V., Davletov K., De Courten B., Degenhardt L., Deiparine S., Deribe K., Deribew A., Dey S., Dicker D., Ding E.L., Djalalinia S., Do H.P., Doku D.T., Douwes-Schultz D., Driscoll T.R., Dubey M., Duncan B.B., Echko M., El-Khatib Z.Z., Ellingsen C.L., Enayati A., Erskine H.E., Eskandarieh S., Esteghamati A., Ermakov S.P., Estep K., Sa Farinha C.S., Faro A., Farzadfar F., Feigin V.L., Fereshtehnejad S.-M., Fernandes J.C., Ferrari A.J., Feyissa T.R., Filip I., Finegold S., Fischer F., Fitzmaurice C., Flaxman A.D., Foigt N., Frank T., Fraser M., Fullman N., Fürst T., Furtado J.M., Gakidou E., Garcia-Basteiro A.L., Gebre T., Gebregergs G.B., Gebrehiwot T.T., Gebremichael D.Y., Geleijnse J.M., Genova-Maleras R., Gesesew H.A., Gething P.W., Gillum R.F., Ginawi I.A.M., Giref A.Z., Giroud M., Giussani G., Godwin W.W., Gold A.L., Goldberg E.M., Gona P.N., Gopalani S.V., Gouda H.N., Goulart A.C., Griswold M., Gupta P.C., Gupta R., Gupta T., Gupta V., Haagsma J.A., Hafezi-Nejad N., Hailu A.D., Hailu G.B., Hamadeh R.R., Hambisa M.T., Hamidi S., Hammami M., Hancock J., Handal A.J., Hankey G.J., Hao Y., Harb H.L., Hareri H.A., Hassanvand M.S., Havmoeller R., Hay S.I., He F., Hedayati M.T., Henry N.J., Heredia-Pi I.B., Herteliu C., Hoek H.W., Horino M., Horita N., Hosgood H.D., Hostiuc S., Hotez P.J., Hoy D.G., Huynh C., Iburg K.M., Ikeda C., Ileanu B.V., Irenso A.A., Irvine C.M.S., Jürisson M., Jacobsen K.H., Jahanmehr N., Jakovljevic M.B., Javanbakht M., Jayaraman S.P., Jeemon P., Jha V., John D., Johnson C.O., Johnson S.C., Jonas J.B., Kabir Z., Kadel R., Kahsay A., Kamal R., Karch A., Karimi S.M., Karimkhani C., Kasaeian A., Kassaw N.A., Kassebaum N.J., Katikireddi S.V., Kawakami N., Keiyoro P.N., Kemmer L., Kesavachandran C.N., Khader Y.S., Khan E.A., Khang Y.-H., Khoja A.T.A., Khosravi A., Khosravi M.H., Khubchandani J., Kieling C., Kievlan D., Kim D., Kim Y.J., Kimokoti R.W., Kinfu Y., Kissoon N., Kivimaki M., Knudsen A.K., Kopec J.A., Kosen S., Koul P.A., Koyanagi A., Defo B.K., Kulikof X.R., Kumar G.A., Kumar P., Kutz M., Kyu H.H., Lal D.K., Lalloo R., Lambert T.L.N., Lan Q., Lansingh V.C., Larsson A., Lee P.H., Leigh J., Leung J., Levi M., Li Y., Kappe D.L., Liang X., Liben M.L., Lim S.S., Liu A., Liu P.Y., Liu Y., Lodha R., Logroscino G., Lorkowski S., Lotufo P.A., Lozano R., Lucas T.C.D., Ma S., Macarayan E.R.K., Maddison E.R., Abd El Razek M.M., Majdan M., Majdzadeh R., Majeed A., Malekzadeh R., Malhotra R., Malta D.C., Manguerra H., Manyazewal T., Mapoma C.C., Marczak L.B., Markos D., Martinez-Raga J., Martins-Melo F.R., Martopullo I., McAlinden C., McGaughey M., McGrath J.J., Mehata S., Meier T., Meles K.G., Memiah P., Memish Z.A., Mengesha M.M., Mengistu D.T., Menota B.G., Mensah G.A., Meretoja A., Meretoja T.J., Millear A., Miller T.R., Minnig S., Mirarefn M., Mirrakhimov E.M., Misganaw A., Mishra S.R., Mohammad K.A., Mohammadi A., Mohammed S., Mokdad A.H., Mola G.L.D., Mollenkopf S.K., Molokhia M., Monasta L., Hernandez J.C.M., Montico M., Mooney M.D., Moradi-Lakeh M., Moraga P., Morawska L., Morrison S.D., Morozof C., Mountjoy-Venning C., Mruts K.B., Muller K., Murthy G.V.S., Musa K.I., Nachega J.B., Naheed A., Naldi L., Nangia V., Nascimento B.R., Nasher J.T., Natarajan G., Negoi I., Ngunjiri J.W., Nguyen C.T., Nguyen G., Nguyen M., Nguyen Q.L., Nguyen T.H., Nichols E., Ningrum D.N.A., Nong V.M., Noubiap J.J.N., Ogbo F.A., Oh I.-H., Okoro A., Olagunju A.T., Olsen H.E., Olusanya B.O., Olusanya J.O., Ong K., Opio J.N., Oren E., Ortiz A., Osman M., Ota E., Mahesh P.A., Pacella R.E., Pakhale S., Pana A., Panda B.K., Jonas S., Papachristou C., Park E.-K., Patten S.B., Patton G.C., Paudel D., Paulson K., Pereira D.M., Perez-Ruiz F., Perico N., Pervaiz A., Petzold M., Phillips M.R., Pigott D.M., Pinho C., Plass D., Pletcher M.A., Polinder S., Postma M.J., Pourmalek F., Purcell C., Qorbani M., Radfar A., Rafay A., Rahimi-Movaghar V., Rahman M., Ur Rahman M.H., Rai R.K., Ranabhat C.L., Rankin Z., Rao P.C., Rath G.K., Rawaf S., Ray S.E., Rehm J., Reiner R.C., Reitsma M.B., Remuzzi G., Rezaei S., Rezai M.S., Rokni M.B., Ronfani L., Roshandel G., Roth G.A., Rothenbacher D., Ruhago G.M., Rizwan S.A., Saadat S., Sachdev P.S., Sadat N., Safdarian M., Saf S., Safiri S., Sagar R., Sahathevan R., Salama J., Salamati P., Salomon J.A., Samy A.M., Sanabria J.R., Sanchez-Niño M.D., Santomauro D., Santos I.S., Milicevic M.M.S., Sartorius B., Satpathy M., Shahraz S., Schmidt M.I., Schneider I.J.C., Schulhofer-Wohl S., Schutte A.E., Schwebel D.C., Schwendicke F., Sepanlou S.G., Servan-Mori E.E., Shackelford K.A., Shaikh M.A., Shamsipour M., Shamsizadeh M., Islam S.M.S., Sharma J., Sharma R., She J., Sheikhbahaei S., Shey M., Shi P., Shields C., Shigematsu M., Shiri R., Shirude S., Shiue I., Shoman H., Shrime M.G., Sigfusdottir I.D., Silpakit N., Silva J.P., Singh A., Singh J.A., Skiadaresi E., Sligar A., Smith A., Smith D.L., Smith M., Sobaih B.H.A., Soneji S., Sorensen R.J.D., Soriano J.B., Sreeramareddy C.T., Srinivasan V., Stanaway J.D., Stathopoulou V., Steel N., Stein D.J., Steiner C., Steinke S., Stokes M.A., Strong M., Strub B., Subart M., Sufyan M.B., Sunguya B.F., Sur P.J., Swaminathan S., Sykes B.L., Tabarés-Seisdedos R., Tadakamadla S.K., Takahashi K., Takala J.S., Talongwa R.T., Tarawneh M.R., Tavakkoli M., Taveira N., Tegegne T.K., Tehrani-Banihashemi A., Temsah M.-H., Terkawi A.S., Thakur J.S., Thamsuwan O., Thankappan K.R., Thomas K.E., Thompson A.H., Thomson A.J., Thrift A.G., Tobe-Gai R., Topor-Madry R., Torre A., Tortajada M., Towbin J.A., Tran B.X., Troeger C., Truelsen T., Tsoi D., Tuzcu E.M., Tyrovolas S., Ukwaja K.N., Undurraga E.A., Updike R., Uthman O.A., Uzochukwu B.S.C., Van Boven J.F.M., Vasankari T., Venketasubramanian N., Violante F.S., Vlassov V.V., Vollset S.E., Vos T., Wakayo T., Wallin M.T., Wang Y.-P., Weiderpass E., Weintraub R.G., Weiss D.J., Werdecker A., Westerman R., Whetter B., Whiteford H.A., Wijeratne T., Wiysonge C.S., Woldeyes B.G., Wolfe C.D.A., Woodbrook R., Workicho A., Xavier D., Xiao Q., Xu G., Yaghoubi M., Yakob B., Yano Y., Yaseri M., Yimam H.H., Yonemoto N., Yoon S.-J., Yotebieng M., Younis M.Z., Zaidi Z., El Sayed Zaki M., Zegeye E.A., Zenebe Z.M., Zerfu T.A., Zhang A.L., Zhang X., Zipkin B., Zodpey S., Lopez A.D., Murray C.J.L., GBD 2016 Causes of Death Collaborators (2017)Background: Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive ...