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Alzheimer's ELAD

Nadav Elad, Bart De Strooper, Sam Lismont, Wim Hagen, Sarah Veugelen, Muriel Arimon, Katrien Horré, Oksana Berezovska, Carsten Sachse, Lucía Chávez-Gutiérrez
The structure and function of the gamma-secretase proteases are of great interest because of their crucial roles in cellular and disease processes. We established a novel purification protocol for the gamma-secretase complex that involves a conformation- and complex-specific nanobody, yielding highly pure and active enzyme. Using single particle electron microscopy, we analyzed the gamma-secretase structure and its conformational variability. Under steady-state conditions, the complex adopts three major conformations, which differ in overall compactness and relative position of the nicastrin ectodomain...
February 1, 2015: Journal of Cell Science
Hermien Acx, Lucía Chávez-Gutiérrez, Lutgarde Serneels, Sam Lismont, Manasi Benurwar, Nadav Elad, Bart De Strooper
γ-Secretase complexes are involved in the generation of amyloid-β (Aβ) in the brain. Therefore, γ-secretase has been proposed as a potential therapeutic target in Alzheimer disease (AD). Targeting γ-secretase activity in AD requires the pharmacological dissociation of the processing of physiological relevant substrates and the generation of "toxic" Aβ. Previous reports suggest the differential targeting of γ-secretase complexes, based on their subunit composition, as a valid strategy. However, little is known about the biochemical properties of the different complexes, and key questions regarding their Aβ product profiles should be first addressed...
February 14, 2014: Journal of Biological Chemistry
Elad Stern, Adaikkan Chinnakkaruppan, Orit David, Nahum Sonenberg, Kobi Rosenblum
Age-associated memory deterioration (and the decline in ability to acquire new information) is one of the major diseases of our era. Cognitive enhancement can be achieved by using psycho-stimulants, such as caffeine or nicotine, but very little is known about drugs that can enhance the consolidation phase of memories in the cortex, the brain structure considered to store, at least partially, long-term memories. We used cortex-dependent taste-learning paradigms to test the hypothesis that pharmacological manipulation of the translation initiation eIF2α, which plays a role in hippocampus-dependent memory, can enhance positive or negative forms of taste memories...
February 6, 2013: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Elad Shemesh, Assaf Rudich, Ilana Harman-Boehm, Tali Cukierman-Yaffe
AIM: Epidemiological and mechanistic studies raised the possibility that cognitive function may be affected by brain responses to insulin. We systematically reviewed and analyzed existing clinical trials that assessed the potential beneficial effects of intranasal insulin administration on cognitive functions. METHODS: Interventional studies measuring changes in cognitive functions in response to intranasal insulin were retrieved and included if they were in English and assessed cognitive functions before and after treatment...
February 2012: Journal of Clinical Endocrinology and Metabolism
P Elad, T A Treves, M Drory, R Verchovsky, S Klimovitsky, S Ben-Laish, S Yaron, K Ginzburg, A D Korczyn
Clinical trials for Alzheimer's disease take place in medical centers all over the world. Patients and caregivers have to decide whether or not to agree to participate in clinical trials. This study aimed to investigate the motivation that determines the caregivers' choice. Nineteen caregivers of demented patients who consented to participate in a clinical trial in our Memory Clinic and 10 caregivers who refused to participate were interviewed. The data were gathered by a self-report questionnaire covering various aspects of the caregivers' decision-making process...
April 2000: International Journal of Geriatric Psychiatry
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