Active gamma-secretase complexes contain only one of each component (2007)
Diehl, Thekla S, Narayanan, Saravanakumar, Funamoto, Satoru, Ihara, Yasuo, ...
Gamma-secretase is an intramembrane aspartyl protease complex that cleaves type I integral membrane proteins, including the amyloid beta-protein precursor and the Notch receptor, and is composed of...
Imhof, Axel, Haass, Christian, Lichtenthaler, Stefan F CORA
Ectodomain shedding and intramembrane proteolysis of the amyloid precursor protein (APP) by alpha-, beta- and gamma-secretase are involved in the pathogenesis of Alzheimer disease (AD). Increased...
Larionov, Sergey, Abramowski, Dorothee, Wiederhold, Karl-Heinz, Yamaguchi, Haruyasu, ...
The deposition of the amyloid beta-protein (Abeta) is a hallmark of Alzheimer's disease (AD). One reason for Abeta-accumulation and deposition in the brain may be an altered drainage along...
European Alzheimer disease funding (2006)
Nitsch, Roger M, Haass, Christian
Centro de Biología Molecular Severo Ochoa.
Mertins, Philipp, Lammich, Sven, Murgia, Marta, Saftig, Paul, ...
Several receptor protein tyrosine phosphatases (RPTPs) are cell adhesion molecules involved in homophilic interactions, suggesting that RPTP outside-in signaling is coupled to cell contact formation....
Capetillo-Zarate, Estibaliz, Staufenbiel, Matthias, Abramowski, Dorothee, Haass, Christian, Escher, Angelika, Stadelmann, Christine, ...
The amyloid β-protein (Aβ) is the main component of Alzheimer's disease-related senile plaques. Although Aβ is associated with the development of Alzheimer's disease, it has not been shown which...
Capetillo-Zarate, Estibaliz, Staufenbiel, Matthias, Abramowski, Dorothee, Haass, Christian, Escher, Angelika, Stadelmann, Christine, ...
The amyloid β-protein (Aβ) is the main component of Alzheimer's disease-related senile plaques. Although Aβ is associated with the development of Alzheimer's disease, it has not been shown which...
Capetillo-Zarate, Estibaliz, Staufenbiel, Matthias, Abramowski, Dorothee, Haass, Christian, Escher, Angelika, Stadelmann, Christine, ...
The amyloid β-protein (Aβ) is the main component of Alzheimer's disease-related senile plaques. Although Aβ is associated with the development of Alzheimer's disease, it has not been shown which...
Smyth, Neil, Borghgraef, Peter, Haass, Christian, ...
The generation of amyloid peptides (Abeta) from the amyloid precursor protein (APP) is initiated by beta-secretase (BACE), whereas subsequent gamma-secretase cleavage mediated by presenilin-1,...
Westmeyer, Gil G, Reiss, Karina, Haass, Christian, Saftig, Paul, ...
The aspartyl protease BACE1 cleaves the amyloid precursor protein and the sialyltransferase ST6Gal I and is important in the pathogenesis of Alzheimer's disease. The normal function of BACE1 and...
Walter, Jochen, Schindzielorz, Alice, Grünberg, Jürgen, Haass, Christian
Mutations within the Presenilin-2 (PS-2) gene are associated with early onset familial Alzheimer’s disease. The gene encodes a polytopic transmembrane protein that undergoes endoproteolytic...
Separation of presenilin function in amyloid β-peptide generation and endoproteolysis of Notch
Kulic, Luka, Walter, Jochen, Multhaup, Gerd, Teplow, David B., Baumeister, Ralf, Romig, Helmut, ...
Most of the genetically inherited Alzheimer's disease cases are caused by mutations in the presenilin genes, PS1 and PS2. PS mutations result in the enhanced production of the highly amyloidogenic...
Tomita, Taisuke, Maruyama, Kei, Saido, Takaomi C., Kume, Hideaki, Shinozaki, Kohki, Tokuhiro, Shinya, ...
To gain insights into the significance of presenilins (PS) in the pathogenetic mechanisms of early-onset familial Alzheimer disease (FAD), we expressed cDNAs for wild-type PS2 and PS2 with the Volga...
Lammich, Sven, Kojro, Elzbieta, Postina, Rolf, Gilbert, Sandra, Pfeiffer, Roland, Jasionowski, Marek, ...
Amyloid β peptide (Aβ), the principal proteinaceous component of amyloid plaques in brains of Alzheimer’s disease patients, is derived by proteolytic cleavage of the amyloid precursor protein...
Walter, Jochen, Grünberg, Jürgen, Capell, Anja, Pesold, Brigitte, Schindzielorz, Alice, Citron, Martin, ...
The majority of familial Alzheimer disease mutations are linked to the recently cloned presenilin (PS) genes, which encode two highly homologous proteins (PS-1 and PS-2). It was shown that the...
Moehlmann, Tobias, Winkler, Edith, Xia, Xuefeng, Edbauer, Dieter, Murrell, Jill, Capell, Anja, ...
The Alzheimer's disease (AD)-associated presenilin (PS) proteins are required for the γ-secretase cleavages of the β-amyloid precursor protein and the site 3 (S3) protease cleavage of Notch. These...
Edbauer, Dieter, Winkler, Edith, Haass, Christian, Steiner, Harald
Amyloid β-peptide (Aβ) is generated by the consecutive cuts of two membrane-bound proteases. β-Secretase cuts at the N terminus of the Aβ domain, whereas γ-secretase mediates the C-terminal cut....
Presenilins mediate a dual intramembranous γ-secretase cleavage of Notch-1
Okochi, Masayasu, Steiner, Harald, Fukumori, Akio, Tanii, Hisashi, Tomita, Taisuke, Tanaka, Toshihisa, ...
Following ectodomain shedding, Notch-1 undergoes presenilin (PS)-dependent constitutive intramembranous endoproteolysis at site-3. This cleavage is similar to the PS-dependent γ-secretase cleavage...
Neumann, Manuela, Kahle, Philipp J., Giasson, Benoit I., Ozmen, Laurence, Borroni, Edilio, Spooren, Will, ...
The pathological modifications of α-synuclein (αS) in Parkinson disease and related diseases are poorly understood. We have detected misfolded αS in situ based on the proteinase K resistance (PK...
Lichtenthaler, Stefan F., Haass, Christian
The amyloid β-peptide (Aβ peptide) is assumed to play a crucial and early role in the pathogenesis of Alzheimer disease. Thus, strategies for a pharmacotherapy aim at reducing Aβ peptide...
Nicalin and its binding partner Nomo are novel Nodal signaling antagonists
Haffner, Christof, Frauli, Mélanie, Topp, Stephanie, Irmler, Martin, Hofmann, Kay, Regula, Jörg T, ...
Nodals are signaling factors of the transforming growth factor-β (TGFβ) superfamily with a key role in vertebrate development. They control a variety of cell fate decisions required for the...
The presenilin C-terminus is required for ER-retention, nicastrin-binding and γ-secretase activity
Kaether, Christoph, Capell, Anja, Edbauer, Dieter, Winkler, Edith, Novak, Bozidar, Steiner, Harald, ...
γ-Secretase is an intramembrane cleaving protease involved in Alzheimer's disease. γ-Secretase occurs as a high molecular weight complex composed of presenilin (PS1/2), nicastrin (NCT), anterior...
Sastre, Magdalena, Steiner, Harald, Fuchs, Klaus, Capell, Anja, Multhaup, Gerd, Condron, Margaret M., ...
The presenilin (PS)-dependent site 3 (S3) cleavage of Notch liberates its intracellular domain (NICD), which is required for Notch signaling. The similar γ-secretase cleavage of the β-amyloid...
Hyperphosphorylation and insolubility of α-synuclein in transgenic mouse oligodendrocytes
Kahle, Philipp J., Neumann, Manuela, Ozmen, Laurence, Müller, Veronika, Jacobsen, Helmut, Spooren, Will, ...
(Oligodendro)glial cytoplasmic inclusions composed of α-synuclein (αSYN) characterize multiple system atrophy (MSA). Mature oligodendrocytes (OLs) do not normally express αSYN, so MSA pathology...
Geling, Andrea, Steiner, Harald, Willem, Michael, Bally-Cuif, Laure, Haass, Christian
Inhibition of amyloid β-peptide (Aβ) production by blocking γ-secretase activity is at present one of the most promising therapeutic strategies to slow progression of Alzheimer’s disease...
Shedding and γ-secretase-mediated intramembrane proteolysis of the mucin-type molecule CD43
Andersson, Christian X., Fernandez-Rodriguez, Julia, Laos, Sirle, Baeckström, Dan, Haass, Christian, Hansson, Gunnar C.
CD43 is a transmembrane molecule that contains a 123-aminoacids-long cytoplasmic tail and a highly O-glycosylated extracellular domain of mucin type. Endogenous CD43 expressed in COLO 205, K562 and...
Take five—BACE and the γ-secretase quartet conduct Alzheimer's amyloid β-peptide generation
In 1959, Dave Brubeck and Paul Desmond revolutionized modern jazz music by composing their unforgettable Take Five in 5/4, one of the most defiant time signatures in all music. Of similar...
Expression of the Alzheimer protease BACE1 is suppressed via its 5′-untranslated region
Lammich, Sven, Schöbel, Susanne, Zimmer, Ann-Katrin, Lichtenthaler, Stefan F, Haass, Christian
The aspartyl protease BACE1 has a pivotal role in the pathogenesis of Alzheimer's disease. Recently, it was shown that in Alzheimer's disease patients, BACE1 levels were elevated although mRNA levels...
How does parkin ligate ubiquitin to Parkinson's disease?
Kahle, Philipp J., Haass, Christian
First in Molecular Medicine Review Series
Anders, Lars, Mertins, Philipp, Lammich, Sven, Murgia, Marta, Hartmann, Dieter, Saftig, Paul, ...
Several receptor protein tyrosine phosphatases (RPTPs) are cell adhesion molecules involved in homophilic interactions, suggesting that RPTP outside-in signaling is coupled to cell contact formation....
Stefanova, Nadia, Reindl, Markus, Neumann, Manuela, Haass, Christian, Poewe, Werner, Kahle, Philipp J., ...
Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by parkinsonism unresponsive to dopaminergic therapy, cerebellar ataxia, and dysautonomia. Neuropathology shows...
Willem, Michael, Dewachter, Ilse, Smyth, Neil, Van Dooren, Tom, Borghgraef, Peter, Haass, Christian, ...
The generation of amyloid peptides (Aβ) from the amyloid precursor protein (APP) is initiated by β-secretase (BACE), whereas subsequent γ-secretase cleavage mediated by presenilin-1, produces Aβ...
Kahle, Philipp J., Neumann, Manuela, Ozmen, Laurence, Müller, Veronika, Odoy, Sabine, Okamoto, Noriko, ...
α-Synuclein (α-SYN) is deposited in intraneuronal cytoplasmic inclusions (Lewy bodies, LBs) characteristic for Parkinson’s disease (PD) and LB dementias. α-SYN forms LB-like fibrils in vitro, in...
Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology
Radde, Rebecca, Bolmont, Tristan, Kaeser, Stephan A, Coomaraswamy, Janaky, Lindau, Dennis, Stoltze, Lars, ...
We have generated a novel transgenic mouse model on a C57BL/6J genetic background that coexpresses KM670/671NL mutated amyloid precursor protein and L166P mutated presenilin 1 under the control of a...
A lipid boundary separates APP and secretases and limits amyloid β-peptide generation
Kaether, Christoph, Haass, Christian
Millions of patients suffer from Alzheimer's disease, and intensive efforts to find a cure for this devastating disorder center on the proteases, which release the deadly amyloid β-peptide from its...
Amyloidogenic processing of the Alzheimer β-amyloid precursor protein depends on lipid rafts
Ehehalt, Robert, Keller, Patrick, Haass, Christian, Thiele, Christoph, Simons, Kai
Formation of senile plaques containing the β-amyloid peptide (Aβ) derived from the amyloid precursor protein (APP) is an invariant feature of Alzheimer's disease (AD). APP is cleaved either by...
Kaether, Christoph, Lammich, Sven, Edbauer, Dieter, Ertl, Michaela, Rietdorf, Jens, Capell, Anja, ...
Amyloid β-peptide (Aβ) is generated by the consecutive cleavages of β- and γ-secretase. The intramembraneous γ-secretase cleavage critically depends on the activity of presenilins (PS1 and PS2)....
Endoplasmic reticulum retention of the γ-secretase complex component Pen2 by Rer1
Kaether, Christoph, Scheuermann, Johanna, Fassler, Matthias, Zilow, Sonja, Shirotani, Keiro, Valkova, Christina, ...
γ-Secretase is involved in the production of amyloid β-peptide, which is the principal component of amyloid plaques in the brains of patients with Alzheimer disease. γ-Secretase is a complex...
The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases
Winklhofer, Konstanze F, Tatzelt, Jörg, Haass, Christian
The etiologies of neurodegenerative diseases may be diverse; however, a common pathological denominator is the formation of aberrant protein conformers and the occurrence of pathognomonic...
A zebrafish model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation
Paquet, Dominik, Bhat, Ratan, Sydow, Astrid, Mandelkow, Eva-Maria, Berg, Stefan, Hellberg, Sven, ...
Our aging society is confronted with a dramatic increase of patients suffering from tauopathies, which include Alzheimer disease and certain frontotemporal dementias. These disorders are...
Parkin Deficiency Delays Motor Decline and Disease Manifestation in a Mouse Model of Synucleinopathy
Fournier, Margot, Vitte, Jérémie, Garrigue, Jérôme, Langui, Dominique, Dullin, Jean-Philippe, Saurini, Françoise, ...
In synucleinopathies, including Parkinson's disease, partially ubiquitylated α-synuclein species phosphorylated on serine 129 (PS129-α-synuclein) accumulate abnormally. Parkin, an ubiquitin-protein...
Fluhrer, Regina, Fukumori, Akio, Martin, Lucas, Grammer, Gudula, Haug-Kröper, Martina, Klier, Bärbel, ...
More than 150 familial Alzheimer disease (FAD)-associated missense mutations in presenilins (PS1 and PS2), the catalytic subunit of the γ-secretase complex, cause aberrant amyloid β-peptide (Aβ)...
Intramembrane Proteolysis by γ-Secretase*
Steiner, Harald, Fluhrer, Regina, Haass, Christian
γ-Secretase mediates the final proteolytic cleavage, which liberates amyloid β-peptide (Aβ), the major component of senile plaques in the brains of Alzheimer disease patients. Therefore,...