ArticleTranslational psychiatry2020
Rivastigmine modifies the α-secretase pathway and potentially early Alzheimer's disease.
Article in Translational psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 78 citations in OpenAlex.
- The Effect of Rivastigmine on Enhanced Glucose Metabolism and Enhanced Synaptic Plasticity in the Hippocampus of Aged Rats: A Sex-Dependent Study.International journal of molecular sciences · 2026Article
- Why acetylcholinesterase inhibitors should be considered disease-modifying drugs for Alzheimer's disease?Aging clinical and experimental research · 2026Review
- Design and synthesis of new phosphazine and triazole derivatives for treatment of Alzheimer's disease: modulating ROS/JNK and Wnt/β-catenin signaling pathways.RSC advances · 2026Article
- BACE-1 and ADAM-10 as Potential Peripheral Biomarkers for Alzheimer's Disease.Current pharmaceutical design · 2026Review
- Computer-aided Drug Design for Alzheimer's Disease: Recent Advancements and Future Perspectives.Current topics in medicinal chemistry · 2026Review
- Phytoconstituents as Potential Therapeutics against Enzymatic Targets for Neurodegenerative Diseases.Current protein & peptide science · 2026Review
- Detecting Mild Cognitive Impairment to Alzheimer's Disease Progression by fMRI Using Convolutional Neural Network and Long-short Term Memory.Basic and clinical neuroscience · 2025Article
- Multi-Target Drug Design in Alzheimer's Disease Treatment: Emerging Technologies, Advantages, Challenges, and Limitations.Pharmacology research & perspectives · 2025Review
- Advancing Care in Alzheimer's Disease: Current Treatments and Their Impact on Quality of Life.Cureus · 2025Review
- A human neuron alzheimer's disease model reveals barriers to senolytic translatability.Alzheimer's research & therapy · 2025Article
- Therapeutic modulation of neurogenesis to improve hippocampal plasticity and cognition in aging and Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Sigma receptors and mitochondria-associated ER membranes are converging therapeutic targets for Alzheimer's disease.Frontiers in neuroscience · 2025Review
- Safety and efficacy of rivastigmine and memantine combined for treatment of patients with Alzheimer's disease: a retrospective study.American journal of translational research · 2025Article
- Evaluating Blood-Brain Barrier Permeability, Cytotoxicity, and Activity of Potential Acetylcholinesterase Inhibitors: In Vitro and In Silico Study.Pharmacology research & perspectives · 2024Article
- Recent Advances in Therapeutics for the Treatment of Alzheimer's Disease.Molecules (Basel, Switzerland) · 2024Review
- Exploring the potential ofJournal of Taibah University Medical Sciences · 2024Article
- Naringenin ameliorates amyloid-β pathology and neuroinflammation in Alzheimer's disease.Communications biology · 2024Article
- Stimulating myelin restoration with BDNF: a promising therapeutic approach for Alzheimer's disease.Frontiers in cellular neuroscience · 2024Review
- Quantifying Personalized Shift-Work Molecular Portraits Underlying Alzheimer's Disease through Computational Biology.The journal of prevention of Alzheimer's disease · 2024Article
- The Amyloid Cascade Hypothesis 2.0 for Alzheimer's Disease and Aging-Associated Cognitive Decline: From Molecular Basis to Effective Therapy.International journal of molecular sciences · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Rivastigmine (or Exelon) is a cholinesterase inhibitor, currently used as a symptomatic treatment for mild-to-moderate Alzheimer's disease (AD). Amyloid-β peptide (Aβ) generated from its precursor protein (APP) by β-secretase (or BACE1) and γ-secretase endoproteolysis. Alternative APP cleavage by α-secretase (a family of membrane-bound metalloproteases- Adamalysins) precludes the generation of toxic Aβ and yields a neuroprotective and neurotrophic secreted sAPPα fragment. Several signal transduction pathways, including protein kinase C and MAP kinase, stimulate α-secretase. We present data to suggest that rivastigmine, in addition to anticholinesterase activity, directs APP processing away from BACE1 and towards α-secretases. We treated rat neuronal PC12 cells and primary human brain (PHB) cultures with rivastigmine and the α-secretase inhibitor TAPI and assayed for levels of APP processing products and α-secretases. We subsequently treated 3×Tg (transgenic) mice with rivastigmine and harvested hippocampi to assay for levels of APP processing products. We also assayed postmortem human control, AD, and AD brains from subjects treated with rivastigmine for levels of APP metabolites. Rivastigmine dose-dependently promoted α-secretase activity by upregulating levels of ADAM-9, -10, and -17 α-secretases in PHB cultures. Co-treatment with TAPI eliminated rivastigmine-induced sAPPα elevation. Rivastigmine treatment elevated levels of sAPPα in 3×Tg mice. Consistent with these results, we also found elevated sAPPα in postmortem brain samples from AD patients treated with rivastigmine. Rivastigmine can modify the levels of several shedding proteins and directs APP processing toward the non-amyloidogenic pathway. This novel property of rivastigmine can be therapeutically exploited for disease-modifying intervention that goes beyond symptomatic treatment for AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.