Article
Neurosciences
Alexandra A. Sandberg, Evan Manning, Heather M. Wilkins, Randall Mazzarino, Taylor Minckley, Russell H. Swerdlow, David Patterson, Yan Qin, Daniel A. Linseman
Summary: In this study, the potential of mitochondrial-targeted AICD to induce neuronal apoptosis and its mechanism of neurotoxicity were examined. The results showed that only when AICD was targeted to the mitochondria, significant neuronal apoptosis was induced. Furthermore, AICD induced apoptosis via a mechanism that is distinct from that of A beta.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Cell Biology
Svenja Koenig, Nadine Schmidt, Karin Bechberger, Sarah Morris, Mercedes Priego, Hannah Zaky, Yuyu Song, Jan Pielage, Silke Brunholz, Scott T. Brady, Stefan Kins, Gerardo Morfini
Summary: This study evaluated the intracellular effects of the amyloid precursor protein (APP) intracellular domain (AICD) on axonal transport. The results showed that AICD inhibits fast axonal transport (FAT), which is a deficit observed in neurons affected by Alzheimer's disease (AD). Further experiments revealed that this inhibitory effect is related to aberrant activation of axonal kinases and phosphorylation of the anterograde motor protein conventional kinesin. Pharmacological inhibitors of these kinases alleviated the inhibitory effect of AICD on FAT. Deletion experiments indicated that this effect requires a sequence encompassing the NPTY motif in AICD and interacting axonal proteins containing a phosphotyrosine-binding domain. These findings provide evidence for axon-specific effects of AICD and suggest a potential mechanistic framework linking alterations in APP processing, FAT deficits, and axonal pathology in AD.
Article
Clinical Neurology
Yinan Yao, Seong Su Kang, Yiyuan Xia, Zhi-Hao Wang, Xia Liu, Thorsten Muller, Yi E. Sun, Keqiang Ye
Summary: The truncated APP C586-695 fragment binds directly to the inflammatory transcription factor CEBPB, enhancing its transcriptional activity and exacerbating Alzheimer's disease-related gene expression and pathogenesis.
Article
Biochemistry & Molecular Biology
Yue Huang, Wenbin Zhang, Xiaorou Guo, Ying Zhang, Junfeng Wu, Hengbing Zu
Summary: In the past 20 years, studies on cell cultures have indicated contradictory findings regarding the relationship between cholesterol levels and amyloid-beta (A beta) production in Alzheimer's disease. This study introduces new cell models induced by DHCR24, which differ from previous models with overexpressed amyloid precursor protein (APP). The results show that cellular cholesterol deficiency increases A beta production, and the disruption of cellular cholesterol homeostasis by APP overexpression might contribute to this effect.
JOURNAL OF LIPID RESEARCH
(2023)
Article
Cell Biology
Magdalena Antonino, Paula Marmo, Carlos Leandro Freites, Gonzalo Emiliano Quassollo, Maria Florencia Sanchez, Alfredo Lorenzo, Elena Anahi Bignante
Summary: Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta (Aβ) in the brain, which is produced by the cleavage of amyloid precursor protein (APP). Aβ assemblies enhance the interaction between APP and BACE1, leading to increased production and accumulation of Aβ. This process involves Aβ-APP/Go signaling and Gβγ subunit signaling.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Xiaotong Wang, Rui Zhou, Xiaqin Sun, Jun Li, Jinxin Wang, Weihua Yue, Lifang Wang, Hesheng Liu, Yigong Shi, Dai Zhang
Summary: This study reveals the mechanism of GM1 in Aβ generation and provides evidence that decreasing GM1 levels represents a potential strategy in AD treatment. GM1 can lead to conformational change in the structure of γ-secretase and accelerate the cleavage of APP, leading to reduced plaque deposition and improved cognitive dysfunction in AD.
Article
Biotechnology & Applied Microbiology
Yen-Chen Liu, Wei-Lun Hsu, Yun-Li Ma, Eminy H. Y. Lee
Summary: The study revealed that AICD SUMOylation enhances its association with binding proteins, facilitates nuclear translocation, and promotes transcriptional activation leading to decreased Aβ levels, oligomerization, and plaque deposits in Alzheimer's disease.
Review
Biochemistry & Molecular Biology
Laura D'Andrea, Ramona Stringhi, Monica Di Luca, Elena Marcello
Summary: Alzheimer's disease is a common neurodegenerative disorder characterized by amyloid deposition and genetic risk factors like the APOEε4 allele. Various proteins related to AD pathogenesis have been found to play roles in the cell nucleus, affecting transcription regulation. Targeting nuclear functions may offer new therapeutic approaches for the disease.
Article
Biochemistry & Molecular Biology
Elissa Afram, Inger Lauritzen, Alexandre Bourgeois, Wejdane El Manaa, Eric Duplan, Mounia Chami, Audrey Valverde, Bauer Charlotte, Raphaelle Pardossi-Piquard, Frederic Checler
Summary: This study identifies eta CTF as a novel APP cleaving enzyme and suggests its involvement in the pathogenesis of Alzheimer's disease. The study also reveals the localization of eta CTF in Golgi and endosomes, as well as its presence in small extracellular vesicles. Furthermore, the expression of eta CTF in APP-null fibroblasts leads to A beta production, implicating its role in amyloid plaque formation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Elnaz Poorgolizadeh, Farshad Homayouni Moghadam, Kianoush Dormiani, Naeimeh Rezaei, Mohammad Hossein Nasr-Esfahani
Summary: Sacubitril/valsartan is the first angiotensin receptor-neprilysin inhibitor drug approved for heart failure by the US and EU, especially recommended for hypertensive heart failure. However, it may cause memory and cognitive dysfunction, and could even exacerbate Alzheimer's disease. More studies are needed to evaluate the safety of Sacubitril/valsartan, particularly its effects on cognitive function long-term.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Laura Schnoeder, Wenqiang Quan, Ye Yu, Inge Tomic, Qinghua Luo, Wenlin Hao, Guoping Peng, Dong Li, Klaus Fassbender, Yang Liu
Summary: In the brains of Alzheimer's disease (AD) mice, deficiency of IKK beta in neurons reduces levels of amyloid-beta-peptide (Aβ) and phosphorylated tau (p-tau), modifies inflammatory activation, and improves cognitive function. The deficiency also decreases BACE1 protein and activity, increases expression of PP2A isoform A, and enhances autophagy. However, the protective effects of IKK beta deficiency differ in APP and tau-transgenic mice. Further studies are needed to understand the interaction between Aβ and p-tau before targeting IKK beta/NF-kappa B for AD therapies.
Article
Multidisciplinary Sciences
Hye Ji Cha, Jie Shen, Jongkyun Kang
Summary: This study investigated the role of the amyloid precursor protein (APP) family in transcriptional regulation. It was found that the mRNA levels of only two APP intracellular c-terminal domain (AICD) target genes were significantly reduced in the cerebral cortex of mice with conditional triple knockout (cTKO) of APP family members. RNA-seq analysis further revealed differential gene expression in the neocortex and hippocampus of cTKO mice, with these genes being involved in various cellular functions.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Luming Zhuang, Chenglin Li, Fei Peng, Elleen Xue, Wenzhe Li, Xinyue Sun, Ping Chen, Qian Zhou, Lei Xue
Summary: Through studying fly AD models, it was found that inhibiting ESCRT components can improve AD-like symptoms induced by APP, suggesting the important role of ESCRT in AD pathogenesis and providing clues for alternative therapeutic strategies for AD.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Medicine, Research & Experimental
Francisco Saez-Orellana, Thomas Leroy, Floriane Ribeiro, Anna Kreis, Karelle Leroy, Fanny Lalloyer, Eric Bauge, Bart Staels, Charles Duyckaerts, Jean-Pierre Brion, Philippe Gailly, Jean-Noel Octave, Nathalie Pierrot
Summary: This study found a possible correlation between lipid metabolism and the onset of Alzheimer's disease. Activation of PPAR alpha showed improvement in synaptic plasticity in AD cases and was inversely related to APP expression. The association was reversed in the case of APP silencing, indicating the key role of PPAR alpha in synaptic activity control.
Article
Biochemistry & Molecular Biology
Amaya Urdanoz-Casado, Javier Sanchez-Ruiz de Gordoa, Maitane Robles, Miren Roldan, Monica Macias Conde, Blanca Acha, Idoia Blanco-Luquin, Maite Mendioroz
Summary: Alzheimer's disease (AD) is the most common cause of age-related dementia. It has been found that a circular RNA (circRNA) derived from the APP gene may contribute to the synthesis of A beta peptides, providing an alternative pathway for A beta biogenesis. In this study, we investigated the expression of a circAPP (hsa_circ_0007556) in the entorhinal cortex of AD patients, and observed decreased levels of circAPP (hsa_circ_0007556) in AD cases compared to controls. We also found a negative correlation between A beta deposits and circAPP (hsa_circ_0007556) and APP expression levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Anna Andrea Lauer, Heike Sabine Grimm, Birgit Apel, Nataliya Golobrodska, Lara Kruse, Elina Ratanski, Noemi Schulten, Laura Schwarze, Thomas Slawik, Saskia Sperlich, Antonia Vohla, Marcus Otto Walter Grimm
Summary: This review summarizes the important role of vitamin B12 in Alzheimer's disease (AD) and discusses potential associations between vitamin B12 deficiency and the disease. Furthermore, it addresses the issues of dietary preferences and medication use leading to B12 deficiency, emphasizing the potential implications for vegetarians and vegans in particular.
Article
Biochemistry & Molecular Biology
Daniel Janitschke, Anna Andrea Lauer, Cornel Manuel Bachmann, Jakob Winkler, Lea Victoria Griebsch, Sabrina Melanie Pilz, Elena Leoni Theiss, Heike Sabine Grimm, Tobias Hartmann, Marcus Otto Walter Grimm
Summary: Alzheimer's disease is characterized by increased plaque formation and tangle accumulation in the brain, along with extensive lipid alterations. Methylxanthines, a type of alkaloid commonly consumed through diet, have been found to interfere with the molecular mechanisms leading to Alzheimer's disease. Our study shows that methylxanthines not only affect triglycerides and cholesterol in the liver and serum, but also induce changes in other lipid classes in neuroblastoma cells. These changes include both beneficial and adverse effects related to Alzheimer's disease. Therefore, we suggest combining methylxanthines with a diet that alters lipid metabolism to counteract the adverse effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Roger A. H. Adan, Francesca Cirulli, Louise Dye, Suzanne Higgs, Kristien Aarts, Eline M. van der Beek, Jan K. Buitelaar, Frederic Destrebecq, Elke De Witte, Tobias Hartmann, Aniko Korosi, Lars Libuda, Suzanne L. Dickson
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Cell Biology
Elena Leoni Theiss, Lea Victoria Griebsch, Anna Andrea Lauer, Daniel Janitschke, Vincent Konrad Johannes Erhardt, Elodie Christiane Haas, Konstantin Nicolas Kuppler, Juliane Radermacher, Oliver Walzer, Dorothea Portius, Heike Sabine Grimm, Tobias Hartmann, Marcus Otto Walter Grimm
Summary: Oxidative stress is linked to Alzheimer's disease, and vitamin B12 deficiency is associated with AD. Vitamin B12 can protect cells from oxidative stress and promote plasmalogen synthesis.
Article
Biochemistry & Molecular Biology
Cornel Manuel Bachmann, Daniel Janitschke, Anna Andrea Lauer, Tobias Erhardt, Tobias Hartmann, Marcus Otto Walter Grimm, Heike Sabine Grimm
Summary: Gemfibrozil, a drug used for over 40 years to reduce triglycerides in blood, induces the transcription of genes for carbohydrate and lipid metabolism. However, little is known about its effects on intracellular lipid-homeostasis, specifically triglycerides. This study showed that gemfibrozil increased intracellular triglycerides in three different cell lines, suggesting enhanced cellular uptake. Furthermore, cell-line specific alterations in acylcarnitines were found, indicating increased transport of fatty acids to mitochondria, potentially important in diseases like Alzheimer's.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Anna A. Lauer, Vu Thu Thuy Nguyen, Daniel Janitschke, Malena dos Santos Guilherme, Cornel M. Bachmann, Heike S. Grimm, Tobias Hartmann, Kristina Endres, Marcus O. W. Grimm
Summary: The administration of acitretin has not been approved for pediatric patients yet. However, it has been found that acitretin can affect the lipid composition in the brain of young mice, potentially leading to hyperlipidemia. This could be detrimental to brain development and maturation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Nutrition & Dietetics
Andrea Thiel, Carina Hermanns, Anna Andrea Lauer, Joerg Reichrath, Tobias Erhardt, Tobias Hartmann, Marcus Otto Walter Grimm, Heike Sabine Grimm
Summary: Lifestyle habits and insufficient sunlight exposure contribute to a high prevalence of vitamin D deficiency, especially in the elderly. Vitamin D supplementation is particularly beneficial for this vulnerable population, as it is associated with various diseases including Alzheimer's disease.
Article
Nutrition & Dietetics
Lea Victoria Griebsch, Elena Leoni Theiss, Daniel Janitschke, Vincent Konrad Johannes Erhardt, Tobias Erhardt, Elodie Christiane Haas, Konstantin Nicolas Kuppler, Juliane Radermacher, Oliver Walzer, Anna Andrea Lauer, Veronika Matschke, Tobias Hartmann, Marcus Otto Walter Grimm, Heike Sabine Grimm
Summary: Due to the global increase in obesity and metabolic disorders, synthetic sweeteners such as aspartame are commonly used as sugar substitutes. However, research suggests that aspartame and its metabolites can cause cellular lipid imbalance and increased oxidative stress, which are important factors in the development of diseases including neurodegenerative diseases like Alzheimer's disease. Therefore, the use of aspartame as a sugar substitute should be reconsidered and its effects on brain metabolism should be studied in vivo.
Article
Clinical Neurology
Suzanne Hendrix, H. Soininen, A. Solomon, P. J. Visser, A. M. J. van Hees, D. S. Counotte, J. Nicodemus-Johnson, S. P. Dickson, K. Blennow, M. Kivipelto, T. Hartmann
Summary: The LipiDiDiet trial evaluated the long term effects of Fortasyn Connect on participants with prodromal AD. The analysis showed that the multinutrient intervention had a significant effect on cognition and global function, as measured by ADCOMS, GST, and BHM. Fortasyn Connect was associated with significantly less clinical decline over 36 months in prodromal AD.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2023)