Results 41 to 50 of about 25,523 (241)

Dual Targeting of Tau Kinases and Autophagy by Abemaciclib Independent of CDK4/6 Inhibition

Advanced Science, EarlyView.
Abemaciclib rescues cognitive function and attenuates tau pathology in Alzheimer's disease models, but not through its known cancer‐fighting mechanism. This study demonstrates that abemaciclib operates independently of CDK4/6 inhibition, instead directly targeting tau kinases CaMKII and GSK3β while simultaneously promoting autophagic clearance of ...
Jihui Han, June‐Hyun Jeong, Dongjoon Lee, Yujin Jung, Yujin Jin, Eun Sun Jung, Haeng Jun Kim, Woo Youn Kim, Chang‐Han Lee, Inhee Mook‐Jung   +9 more
wiley   +1 more source

Autophagy Activators Normalize Aberrant Tau Proteostasis and Rescue Synapses in Human Familial Alzheimer's Disease iPSC‐Derived Cortical Organoids

Advanced Science, EarlyView.
A new cerebrocortical organoid model using isogenic hiPSCs with familial Alzheimer's mutations recapitulates key AD features, including amyloid‐beta and phospho‐Tau aggregation, neuronal hyperexcitability, and synapse loss. Single‐cell RNA‐seq reveals aberrant pathways in excitatory and inhibitory neurons.
Sergio R. Labra, Jadon Compher, Akhil Prabhavalkar, Mireya Almaraz, Claudia Cedeño Kwong, Christine Baal, Maria Talantova, Nima Dolatabadi, Julian Piña‐Sanz, Yubo Wang, Leonard Yoon, Swagata Ghatak, Zi Gao, Yuting Zhang, Dorit Trudler, Lynee Massey, Wei Lin, Anthony Balistreri, Michael Bula, Nicholas J. Schork, Tony S. Mondala, Steven R. Head, Jeffery W. Kelly, Stuart A. Lipton   +23 more
wiley   +1 more source

Presenilin mutations deregulate mitochondrial Ca2+ homeostasis and metabolic activity causing neurodegeneration in Caenorhabditis elegans

eLife, 2018
Mitochondrial dysfunction and subsequent metabolic deregulation is observed in neurodegenerative diseases and aging. Mutations in the presenilin (PSEN) encoding genes (PSEN1 and PSEN2) cause most cases of familial Alzheimer’s disease (AD); however, the ...
Shaarika Sarasija, Jocelyn T Laboy, Zahra Ashkavand, Jennifer Bonner, Yi Tang, Kenneth R Norman   +5 more
doaj   +1 more source

Macrophage TRIM21 Inhibition Ameliorates Murine Acute Pancreatitis via PHB2‐Mediated Mitochondrial Stabilization

Advanced Science, EarlyView.
Macrophage‐derived TRIM21 drives the progression of AP via ubiquitin‐proteasome‐mediated degradation of PHB2, leading to impaired PHB2‐mediated mitophagy. Therefore, accumulation of cytosolic mtDNA hyperactivates the cGAS‐STING signaling axis, thereby amplifying inflammatory cascades.
Yansong Xu, Yuansong Sun, Xin Zhou, Kai Song, Chunlin Yin, Zhaohua Wang, Fei Xie, He Li   +7 more
wiley   +1 more source

Mitophagy and Ubiquitination Coordinate Context‐Specific Mitochondrial Quality Control and EMT/MET Plasticity to Drive Cancer Cell Invasion

Advanced Science, EarlyView.
Metastatic invasion emerges when tumor‐intrinsic programs and microenvironmental forces converge on mitochondrial quality control. A context‐stratified framework links mtROS, mtDNA integrity, mechanics and nutrient/oxygen cues to fission–fusion remodeling, mtUPR and mitophagy.
Bin‐Hsu Mao, Bo‐Kai Su, Ying‐Jan Wang, Ting‐Yuan Tu   +3 more
wiley   +1 more source

Protein Topology of Presenilin 1 [PDF]

Neuron, 1996
Mutations in a gene encoding a multitransmembrane protein, termed presenilin 1 (PS1), are causative in the majority of early-onset cases of AD. To determine the topology of PS1, we utilized two strategies: first, we tested whether putative transmembranes are sufficient to export a protease-sensitive substrate across a lipid bilayer; and second, we ...
Doan, Andrew, Thinakaran, Gopal, Borchelt, David R, Slunt, Hilda H, Ratovitsky, Tamara, Podlisny, Marcia, Selkoe, Dennis J, Seeger, Mary, Gandy, Samuel E, Price, Donald L, Sisodia, Sangram S   +10 more
openaire   +2 more sources

Association of active γ-secretase complex with lipid rafts

Journal of Lipid Research, 2005
Cholesterol has been implicated in the pathogenesis of Alzheimer's disease (AD). Although the underlying mechanisms are not yet clear, several studies have provided evidence for the involvement of cholesterol-rich lipid rafts in the production of amyloid
Yasuomi Urano, Ikuo Hayashi, Noriko Isoo, Patrick C. Reid, Yoshikazu Shibasaki, Noriko Noguchi, Taisuke Tomita, Takeshi Iwatsubo, Takao Hamakubo, Tatsuhiko Kodama   +9 more
doaj   +1 more source

Polyphenol diet and exercise as neuroprotective factors in a Drosophila model of Alzheimer's disease

Animal Models and Experimental Medicine, EarlyView.
Moderate exercise and low‐dose ellagic acid supplementation improved motor performance, learning, and longevity in a transgenic Drosophila model of Alzheimer's disease. Both interventions showed hormetic effects—that is, beneficial at low levels, but detrimental at higher intensities or doses.
Michelle Morgan, Zaida Lopez Rodriguez, Richard E. Hartman   +2 more
wiley   +1 more source

The presenilins and Alzheimer's disease [PDF]

Human Molecular Genetics, 1997
The presenilin 1 and presenilin 2 genes have been identified as pathogenic loci involved in the majority of early onset, autosomal dominant Alzheimer's disease. A series of (predominantly) missense mutations have been identified in the two genes which lead to disease. The presenilins are probably eight transmembrane domain proteins with both termini in
M, Hutton, J, Hardy
openaire   +2 more sources

Increased expression of inflammasome signaling genes and proteins in selective brain regions in the intermediate stage of Alzheimer's disease

Brain Pathology, EarlyView.
Neuritic plaques increase in the intermediate stage of Alzheimer's neuropathological change. The intermediate stage of Alzheimer's disease was investigated by transcriptomics and immunohistochemistry. This revealed that inflammasome sensors NLRP1, NLRP3, and AIM2 oligomerize with ASC speck to form the inflammasome complex and initiate the downstream ...
Juan Pablo de Rivero Vaccari, David A. Davis, Andrew P. Sawaya, Susanna P. Garamszegi, Xiaoyan Sun, Ayled Barreda, Helen M. Bramlett, Sakir Humayun Gultekin, W. Dalton Dietrich, Robert W. Keane, Regina T. Vontell   +10 more
wiley   +1 more source