Enzyme-substrate interface targeting by imidazole-based γ-secretase modulators activates γ-secretase and stabilizes its interaction with APP.
The Embo Journal
Petit, Dieter D; Hitzenberger, Manuel M; Koch, Matthias M; Lismont, Sam S; Zoltowska, Katarzyna Marta KM; Enzlein, Thomas T; Hopf, Carsten C; Zacharias, Martin M; Chávez-Gutiérrez, Lucía L
Preferential Involvement of BRCA1/BARD1, Not Tip60/Fe65, in DNA Double-Strand Break Repair in Presenilin-1 P117L Alzheimer Models.
Neural Plasticity
Authiat, Marcella M MM; Gruz-Gibelli, Emmanuelle E; Colas, Julien J; Bianchi, Estelle E; Garcia-Arauzo, Marta M; Marin, Pascale P; Herrmann, François R FR; Savioz, Armand A
Individual and combined presenilin 1 and 2 knockouts reveal that both have highly overlapping functions in HEK293T cells.
The Journal Of Biological Chemistry
Lessard, Christian B CB; Rodriguez, Edgardo E; Ladd, Thomas B TB; Minter, Lisa M LM; Osborne, Barbara A BA; Miele, Lucio L; Golde, Todd E TE; Ran, Yong Y
APP-Mediated Signaling Prevents Memory Decline in Alzheimer's Disease Mouse Model.
Cell Reports
Deyts, Carole C; Clutter, Mary M; Pierce, Nicholas N; Chakrabarty, Paramita P; Ladd, Thomas B TB; Goddi, Anna A; Rosario, Awilda M AM; Cruz, Pedro P; Vetrivel, Kulandaivelu K; Wagner, Steven L SL; Thinakaran, Gopal G; Golde, Todd E TE; Parent, Angèle T AT
Proteolytic Processing of Neurexins by Presenilins Sustains Synaptic Vesicle Release.
The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience
Servián-Morilla, Emilia E; Robles-Lanuza, Estefanía E; Sánchez-Hidalgo, Ana C AC; Camacho-Garcia, Rafael J RJ; Paez-Gomez, Juan A JA; Mavillard, Fabiola F; Saura, Carlos A CA; Martinez-Mir, Amalia A; Scholl, Francisco G FG
Mutational re-modeling of di-aspartyl intramembrane proteases: uncoupling physiologically-relevant activities from those associated with Alzheimer's disease.
Oncotarget
Grigorenko, Anastasia P AP; Moliaka, Youri K YK; Plotnikova, Olga V OV; Smirnov, Alexander A; Nikishina, Vera A VA; Goltsov, Andrey Y AY; Gusev, Fedor F; Andreeva, Tatiana V TV; Nelson, Omar O; Bezprozvanny, Ilya I; Rogaev, Evgeny I EI
Mapping the Binding Site of BMS-708163 on γ-Secretase with Cleavable Photoprobes.
Cell Chemical Biology
Gertsik, Natalya N; Am Ende, Christopher W CW; Geoghegan, Kieran F KF; Nguyen, Chuong C; Mukherjee, Paramita P; Mente, Scot S; Seneviratne, Uthpala U; Johnson, Douglas S DS; Li, Yue-Ming YM
Generation and deposition of Aβ43 by the virtually inactive presenilin-1 L435F mutant contradicts the presenilin loss-of-function hypothesis of Alzheimer's disease.
Embo Molecular Medicine
Kretner, Benedikt B; Trambauer, Johannes J; Fukumori, Akio A; Mielke, Janina J; Kuhn, Peer-Hendrik PH; Kremmer, Elisabeth E; Giese, Armin A; Lichtenthaler, Stefan F SF; Haass, Christian C; Arzberger, Thomas T; Steiner, Harald H
Dysregulation of Nutrient Sensing and CLEARance in Presenilin Deficiency.
Cell Reports
Reddy, Kavya K; Cusack, Corey L CL; Nnah, Israel C IC; Khayati, Khoosheh K; Saqcena, Chaitali C; Huynh, Tuong B TB; Noggle, Scott A SA; Ballabio, Andrea A; Dobrowolski, Radek R
γ-Secretase directly sheds the survival receptor BCMA from plasma cells.
Nature Communications
Laurent, Sarah A SA; Hoffmann, Franziska S FS; Kuhn, Peer-Hendrik PH; Cheng, Qingyu Q; Chu, Yuanyuan Y; Schmidt-Supprian, Marc M; Hauck, Stefanie M SM; Schuh, Elisabeth E; Krumbholz, Markus M; Rübsamen, Heike H; Wanngren, Johanna J; Khademi, Mohsen M; Olsson, Tomas T; Alexander, Tobias T; Hiepe, Falk F; Pfister, Hans-Walter HW; Weber, Frank F; Jenne, Dieter D; Wekerle, Hartmut H; Hohlfeld, Reinhard R; Lichtenthaler, Stefan F SF; Meinl, Edgar E
Cellular FLICE-like Inhibitory Protein (c-FLIP) and PS1-associated Protein (PSAP) Mediate Presenilin 1-induced γ-Secretase-dependent and -independent Apoptosis, Respectively.
The Journal Of Biological Chemistry
Zeng, Linlin L; Hu, Chen C; Zhang, Fuqiang F; Xu, Daniel C DC; Cui, Mei-Zhen MZ; Xu, Xuemin X
Presenilin transmembrane domain 8 conserved AXXXAXXXG motifs are required for the activity of the γ-secretase complex.
The Journal Of Biological Chemistry
Marinangeli, Claudia C; Tasiaux, Bernadette B; Opsomer, Rémi R; Hage, Salim S; Sodero, Alejandro O AO; Dewachter, Ilse I; Octave, Jean Noël JN; Smith, Steven O SO; Constantinescu, Stefan N SN; Kienlen-Campard, Pascal P
An ancestral non-proteolytic role for presenilin proteins in multicellular development of the social amoeba Dictyostelium discoideum.
Journal Of Cell Science
Ludtmann, Marthe H R MH; Otto, Grant P GP; Schilde, Christina C; Chen, Zhi-Hui ZH; Allan, Claire Y CY; Brace, Selina S; Beesley, Philip W PW; Kimmel, Alan R AR; Fisher, Paul P; Killick, Richard R; Williams, Robin S B RS
Pozdnyakov, Nikolay N; Murrey, Heather E HE; Crump, Christina J CJ; Pettersson, Martin M; Ballard, T Eric TE; Am Ende, Christopher W CW; Ahn, Kwangwook K; Li, Yue-Ming YM; Bales, Kelly R KR; Johnson, Douglas S DS
Hyperphosphorylation of Tau induced by naturally secreted amyloid-β at nanomolar concentrations is modulated by insulin-dependent Akt-GSK3β signaling pathway.
Upregulated function of mitochondria-associated ER membranes in Alzheimer disease.
The Embo Journal
Area-Gomez, Estela E; Del Carmen Lara Castillo, Maria M; Tambini, Marc D MD; Guardia-Laguarta, Cristina C; de Groof, Ad J C AJ; Madra, Moneek M; Ikenouchi, Junichi J; Umeda, Masato M; Bird, Thomas D TD; Sturley, Stephen L SL; Schon, Eric A EA
Presenilins promote the cellular uptake of copper and zinc and maintain copper chaperone of SOD1-dependent copper/zinc superoxide dismutase activity.
The Journal Of Biological Chemistry
Greenough, Mark A MA; Volitakis, Irene I; Li, Qiao-Xin QX; Laughton, Katrina K; Evin, Genevieve G; Ho, Michael M; Dalziel, Andrew H AH; Camakaris, James J; Bush, Ashley I AI
Presenilin 1 mutants impair the self-renewal and differentiation of adult murine subventricular zone-neuronal progenitors via cell-autonomous mechanisms involving notch signaling.
The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience
Veeraraghavalu, Karthikeyan K; Choi, Se Hoon SH; Zhang, Xiaoqiong X; Sisodia, Sangram S SS
Functional analysis of the transmembrane domains of presenilin 1: participation of transmembrane domains 2 and 6 in the formation of initial substrate-binding site of gamma-secretase.
The large hydrophilic loop of presenilin 1 is important for regulating gamma-secretase complex assembly and dictating the amyloid beta peptide (Abeta) Profile without affecting Notch processing.
The Journal Of Biological Chemistry
Wanngren, Johanna J; Frånberg, Jenny J; Svensson, Annelie I AI; Laudon, Hanna H; Olsson, Fredrik F; Winblad, Bengt B; Liu, Frank F; Näslund, Jan J; Lundkvist, Johan J; Karlström, Helena H
APH1 polar transmembrane residues regulate the assembly and activity of presenilin complexes.
The Journal Of Biological Chemistry
Pardossi-Piquard, Raphaëlle R; Yang, Seung-Pil SP; Kanemoto, Soshi S; Gu, Yongjun Y; Chen, Fusheng F; Böhm, Christopher C; Sevalle, Jean J; Li, Tong T; Wong, Philip C PC; Checler, Frédéric F; Schmitt-Ulms, Gerold G; St George-Hyslop, Peter P; Fraser, Paul E PE
ADAM10, the rate-limiting protease of regulated intramembrane proteolysis of Notch and other proteins, is processed by ADAMS-9, ADAMS-15, and the gamma-secretase.
The Journal Of Biological Chemistry
Tousseyn, Thomas T; Thathiah, Amantha A; Jorissen, Ellen E; Raemaekers, Tim T; Konietzko, Uwe U; Reiss, Karina K; Maes, Elke E; Snellinx, An A; Serneels, Lutgarde L; Nyabi, Omar O; Annaert, Wim W; Saftig, Paul P; Hartmann, Dieter D; De Strooper, Bart B
Impairments in fast axonal transport and motor neuron deficits in transgenic mice expressing familial Alzheimer's disease-linked mutant presenilin 1.
The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience
Lazarov, Orly O; Morfini, Gerardo A GA; Pigino, Gustavo G; Gadadhar, Archana A; Chen, Xiangjun X; Robinson, John J; Ho, Hanson H; Brady, Scott T ST; Sisodia, Sangram S SS
The GxGD motif of presenilin contributes to catalytic function and substrate identification of gamma-secretase.
The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience
Yamasaki, Aya A; Eimer, Stefan S; Okochi, Masayasu M; Smialowska, Agata A; Kaether, Christoph C; Baumeister, Ralf R; Haass, Christian C; Steiner, Harald H
Spatial segregation of gamma-secretase and substrates in distinct membrane domains.
The Journal Of Biological Chemistry
Vetrivel, Kulandaivelu S KS; Cheng, Haipeng H; Kim, Seong-Hun SH; Chen, Ying Y; Barnes, Natalie Y NY; Parent, Angèle T AT; Sisodia, Sangram S SS; Thinakaran, Gopal G
Familial Alzheimer's disease presenilin 1 mutations cause alterations in the conformation of presenilin and interactions with amyloid precursor protein.
The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience
Berezovska, Oksana O; Lleo, Alberto A; Herl, Lauren D LD; Frosch, Matthew P MP; Stern, Edward A EA; Bacskai, Brian J BJ; Hyman, Bradley T BT