The early embryonic lethality of mutant mice bearing germ-line deletions of both presenilin genes precluded the study of their functions in neural development. We therefore employed the Cre-loxP technology to gen...
The early stages of Alzheimer's disease (AD) are closely associated with the production of the Aβ1–42 peptide, loss of synapses and gradual cognitive decline. Since some epidemiological studies showed that EGb 76...
Authors: Clive Bate, Mourad Tayebi and Alun Williams
Shedding of the Alzheimer amyloid precursor protein (APP) ectodomain can be accelerated by phorbol esters, compounds that act via protein kinase C (PKC) or through unconventional phorbol-binding proteins such ...
Authors: Annat F Ikin, Mirsada Causevic, Steve Pedrini, Lyndsey S Benson, Joseph D Buxbaum, Toshiharu Suzuki, Simon Lovestone, Shigeki Higashiyama, Tomas Mustelin, Robert D Burgoyne and Sam Gandy
The pathogenesis of Alzheimer's disease is highly complex. While several pathologies characterize this disease, amyloid plaques, composed of the β-amyloid peptide are hallmark neuropathological lesions in Alzh...
Mice carrying the spontaneous genetic mutation known as Wallerian degeneration slow (Wlds) have a unique neuroprotective phenotype, where axonal and synaptic compartments o...
Authors: Thomas M Wishart, Stephen HF MacDonald, Philip E Chen, Michael J Shipston, Michael P Coleman, Thomas H Gillingwater and Richard R Ribchester
Recent studies demonstrate that in addition to its modulatory effect on APP processing, in vivo application of Liver X Receptor agonist T0901317 (T0) to APP transgenic and non-transgenic mice decreases the level ...
Authors: Iliya Lefterov, Angie Bookout, Zhu Wang, Matthias Staufenbiel, David Mangelsdorf and Radosveta Koldamova
Genetically engineered neural stem cell (NSC) lines are promising vectors for the treatment of neurodegenerative diseases, particularly Parkinson's disease (PD). Neurturin (NTN), a member of the glial cell lin...
Authors: Wei-Guo Liu, Xi-Jing Wang, Guo-Qiang Lu, Biao Li, Gang Wang and Sheng-Di Chen
Amyloid-related degenerative diseases are associated with the accumulation of misfolded proteins as amyloid fibrils in tissue. In Alzheimer disease (AD), amyloid accumulates in several distinct types of insolu...
Authors: Rakez Kayed, Elizabeth Head, Floyd Sarsoza, Tommy Saing, Carl W Cotman, Mihaela Necula, Lawrence Margol, Jessica Wu, Leonid Breydo, Jennifer L Thompson, Suhail Rasool, Tatyana Gurlo, Peter Butler and Charles G Glabe
Alzheimer's disease (AD) is characterized by the presence of two histopathological hallmarks; the senile plaques, or extracellular deposits mainly composed of amyloid-β peptide (Aβ), and the neurofibrillary ta...
Authors: Ismael Santa-Maria, Félix Hernández, Joaquín Del Rio, Francisco J Moreno and Jesús Avila
The strain of MeCP2tm1.1Bird mice is a broadly used model for Rett syndrome. Because males carrying the invalidated MeCP2 locus are sterile, this strain has to be maintained in a heterozygous state. All animals t...
Authors: Julie Miralvès, Eddy Magdeleine and Etienne Joly
A central event in Alzheimer's disease (AD) is the regulated intramembraneous proteolysis of the β-amyloid precursor protein (APP), to generate the β-amyloid (Aβ) peptide and the APP intracellular domain (AICD...
Authors: Can Zhang, Preeti J Khandelwal, Ranjita Chakraborty, Trinna L Cuellar, Srikant Sarangi, Shyam A Patel, Christopher P Cosentino, Michael O'Connor, Jeremy C Lee, Rudolph E Tanzi and Aleister J Saunders
The generation of the amyloid-β peptide (Aβ) through the proteolytic processing of the amyloid precursor protein (APP) is a central event in the pathogenesis of Alzheimer's disease (AD). Recent studies highlig...
Authors: Rodrigo A Fuentealba, Maria Ines Barría, Jiyeon Lee, Judy Cam, Claudia Araya, Claudia A Escudero, Nibaldo C Inestrosa, Francisca C Bronfman, Guojun Bu and Maria-Paz Marzolo
John Finberg is a professor of pharmacology at the Faculty of Medicine, Technion – Israel Institute of Technology, home of Israel's two Nobel laureates. He and his colleague Prof. Moussa Youdim were instrument...
Neurofibrillary tangles (NFTs) are intraneuronal aggregates associated with several neurodegenerative diseases including Alzheimer's disease. These abnormal accumulations are primarily comprised of fibrils of ...
Authors: Carolyn A Rankin, Qian Sun and Truman C Gamblin
Alzheimer's disease (AD) is characterized by a decline in cognitive function and accumulation of amyloid-β peptide (Aβ) in extracellular plaques. Mutations in amyloid precursor protein (APP) and presenilins al...
Authors: Patricia A Lawlor, Ross J Bland, Pritam Das, Robert W Price, Vallie Holloway, Lisa Smithson, Bridget L Dicker, Matthew J During, Deborah Young and Todd E Golde
Parkinson's disease is the most common movement disorder characterized by dopaminergic dysfunction and degeneration. Loss-of-function mutations in the DJ-1 gene have been linked to autosomal recessive forms of ea...
Since the majority of apolipoprotein E (apoE) existing in the cerebrospinal fluid is associated with high-density lipoprotein (HDL), one should focus on the role of the apoE-HDL complex rather than on that of ...
Authors: Jian-Sheng Gong, Shin-ya Morita, Mariko Kobayashi, Tetsurou Handa, Shinobu C Fujita, Katsuhiko Yanagisawa and Makoto Michikawa
A critical issue in understanding Huntington's disease (HD) pathogenesis is how the ubiquitously expressed mutant huntingtin (mhtt) with an expanded polyglutamine repeat can cause selective toxicity of striata...
Authors: Xiaofeng Gu, Véronique M André, Carlos Cepeda, Shi-Hua Li, Xiao-Jiang Li, Michael S Levine and X William Yang
Animal studies suggest that brain apolipoprotein E (apoE) levels influence amyloid-β (Aβ) deposition and thus risk for Alzheimer's disease (AD). We have previously demonstrated that deletion of the ATP-binding...
Authors: Suzanne E Wahrle, Aarti R Shah, Anne M Fagan, Scott Smemo, John SK Kauwe, Andrew Grupe, Anthony Hinrichs, Kevin Mayo, Hong Jiang, Leon J Thal, Alison M Goate and David M Holtzman
α-synuclein is a small soluble, cytosolic protein which associates with vesicular membranes. It is a component of intracellular Lewy bodies present in Parkinson's disease and a subset of Alzheimer's disease (A...
Authors: Verena Kallhoff, Erica Peethumnongsin and Hui Zheng
The pathological hallmarks of transmissible spongiform encephalopathy (TSE) diseases are the deposition of a misfolded form of a host-encoded protein (PrPres), marked astrocytosis, microglial activation and spong...
Authors: Michael J Stobart, Debra Parchaliuk, Sharon LR Simon, Jillian LeMaistre, Jozef Lazar, Richard Rubenstein and J David Knox
Alzheimer's disease (AD) is characterized by cerebral deposition of β-amyloid (Aβ) peptides. Aβ is released from ectodomain cleaved amyloid precursor protein (APP) via intramembranous proteolysis by γ-secretas...
Authors: Kulandaivelu S Vetrivel, Ping Gong, James W Bowen, Haipeng Cheng, Ying Chen, Meghan Carter, Phuong D Nguyen, Lisa Placanica, Felix T Wieland, Yue-Ming Li, Maria Z Kounnas and Gopal Thinakaran
The β-amyloid precursor protein (APP) is sequentially cleaved by the β- and then γ-secretase to generate the amyloid β-peptides Aβ40 and Aβ42. Increased Aβ42/Aβ40 ratios trigger amyloid plaque formations in Al...
Authors: Yuzhi Chen, Angela M Bodles, Donna L McPhie, Rachael L Neve, Robert E Mrak and W Sue T Griffin
Inflammation and oxidative stress are both involved in the pathogenesis of Alzheimer disease and have been shown to be reciprocally linked. One group of molecules that have been directly associated with inflam...
Authors: Gemma Casadesus, Mark A Smith, Samar Basu, Jing Hua, Dae E Capobianco, Sandra L Siedlak, Xiongwei Zhu and George Perry
Recent attention has focused on understanding the role of the brain-renin-angiotensin-system (RAS) in stroke and neurodegenerative diseases. Direct evidence of a role for the brain-RAS in Parkinson's disease (...
Authors: Tom N Grammatopoulos, Susan M Jones, Ferogh A Ahmadi, Brian R Hoover, Lawrence D Snell, Jesse Skoch, Vimal V Jhaveri, Andy M Poczobutt, James A Weyhenmeyer and W Michael Zawada
Huntington disease (HD) is caused by expansion of a polyglutamine (polyQ) domain in the protein known as huntingtin (htt), and the disease is characterized by selective neurodegeneration. Expansion of the poly...
Apolipoprotein E (apoE) receptors act as signaling molecules in neurons, altering phosphorylation of numerous proteins after extracellular ligand binding and affecting neurite outgrowth, synapse formation, and...
Authors: Hyang-Sook Hoe, Jacob Freeman and G William Rebeck
Mutations in LRRK2 encoding leucine-rich repeat kinase 2 are thus far the most frequent genetic cause associated with autosomal dominant and idiopathic Parkinson's disease (PD). To examine whether LRRK2 is direct...
Authors: Xiongwei Zhu, Asim Babar, Sandra L Siedlak, Qiwei Yang, Genta Ito, Takeshi Iwatsubo, Mark A Smith, George Perry and Shu G Chen
Signal peptide peptidase (SPP) is an intramembrane cleaving protease identified by its cleavage of several type II membrane signal peptides. Conservation of intramembrane active site residues demonstrates that...
Authors: Andrew C Nyborg, Lauren Herl, Oksana Berezovska, Anne V Thomas, Thomas B Ladd, Karen Jansen, Bradley T Hyman and Todd E Golde
More than a decade has passed since apolipoprotein E4 (APOE-ε4) was identified as a primary risk factor for Alzheimer 's disease (AD), yet researchers are even now struggling to understand how the apolipoprotein ...
Authors: G William Rebeck, Mary Jo LaDu, Steven Estus, Guojun Bu and Edwin J Weeber
Alzheimer disease (AD) is clinically characterized by progressive memory loss, impairments in behavior, language and visual-spatial skills and ultimately, death. Epidemiological data reporting the predispositi...
Authors: Kate M Webber, Douglas M Stocco, Gemma Casadesus, Richard L Bowen, Craig S Atwood, Laura A Previll, Peggy LR Harris, Xiongwei Zhu, George Perry and Mark A Smith
Amyloid β is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene, encoding for P-gp, is highly polymorphic and this may result ...
Authors: Suzanne V Frankfort, Valerie D Doodeman, Remco Bakker, Linda R Tulner, Jos PCM van Campen, Paul HM Smits and Jos H Beijnen
Selenium is an essential micronutrient that function through selenoproteins. Selenium deficiency results in lower concentrations of selenium and selenoproteins. The brain maintains it's selenium better than ot...
Authors: Melinda M Peters, Kristina E Hill, Raymond F Burk and Edwin J Weeber
Radon is a ubiquitous noble gas in the environment and a primary source of harmful radiation exposure for humans; it decays in a cascade of daughters (RAD) by releasing the cell damaging high energy alpha part...
Authors: Berislav Momčilović, Glenn I Lykken and Marvin Cooley
Over 5,000 participants attended the 10th International Conference on Alzheimer's Disease (ICAD) and Related Disorders in Madrid, Spain from July 15–20, 2006. Highlights of the conference included reports on b...
Cognitive performance declines with increasing age. Possible cellular mechanisms underlying this age-related functional decline remain incompletely understood. Early studies attributed this functional decline ...
Authors: Mingbo Han, Frank Schottler, Debin Lei, Elizabeth Y Dong, Alexander Bryan and Jianxin Bao
Amyloid-β peptide (Aβ) accumulation in the brain is an early, toxic event in the pathogenesis of Alzheimer's disease (AD). Aβ is produced by proteolytic processing of a transmembrane protein, β-amyloid precurs...
Aberrant hyperphosphorylation of tau protein has been implicated in a variety of neurodegenerative disorders. Although a number of protein kinases have been shown to phosphorylate tau in vitro and in vivo, the mo...
Authors: Xue Zhang, Yun-wu Zhang, Shijie Liu, Ayelen Bulloj, Gary G Tong, Zhuohua Zhang, Francesca-Fang Liao and Huaxi Xu
The microtubule-associated protein tau (MAPT) is a pathological component of several neurodegenerative diseases and clinical dementias. Here, we have investigated the effects of a series of commercially availa...
Authors: Chad A Dickey, Peter Ash, Natalia Klosak, Wing C Lee, Leonard Petrucelli, Michael Hutton and Christopher B Eckman
The amyloid precursor protein (APP) takes a central position in Alzheimer's disease (AD) pathogenesis: APP processing generates the β-amyloid (Aβ) peptides, which are deposited as the amyloid plaques in brains...
Mutations in PSEN1 and PSEN2 genes account for the majority of cases of early-onset familial Alzheimer disease. Since the first prediction of a genetic link between PSEN1 and PSEN2 with Alzheimer's disease, many ...
Authors: Kulandaivelu S Vetrivel, Yun-wu Zhang, Huaxi Xu and Gopal Thinakaran
The mammalian Vps10p sorting receptor family is a group of 5 type I membrane homologs (Sortilin, SorLA, and SorCS1-3). These receptors bind various cargo proteins via their luminal Vps10p domains and have been...
Authors: Andrew C Nyborg, Thomas B Ladd, Craig W Zwizinski, James J Lah and Todd E Golde
Presenilin-dependent γ-secretase cleavage of several transmembrane proteins, including amyloid-β precursor protein and Notch, mediates the intramembrane proteolysis to liberate their intracellular domains that...
Authors: Taisuke Tomita, Sayaka Tanaka, Yuichi Morohashi and Takeshi Iwatsubo
Despite the existence of several scientific journals that publish research papers and reviews related to neurodegenerative diseases, a journal specifically devoted to the molecular and cellular aspects of dise...
