ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
Protection against the synaptic targeting and toxicity of Alzheimer's-associated Aβ oligomers by insulin mimetic chiro-inositols.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 55 citations in OpenAlex.
- Vitamin deficiencies and Alzheimer's disease: evidence and implications for supplementation.Frontiers in nutrition · 2026Review
- Physiological roles of phosphoinositides and inositol phosphates: Implications for metabolic dysfunction-associated steatotic liver disease.Clinical science (London, England : 1979) · 2025Review
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- L-quebrachitol Modulates the Anti-convulsant Effects of Carbamazepine Possibly Through Voltage-gated Sodium Channel Blocking Mechanism in Chicks: In Vivo and In Silico Studies.Brain and behavior · 2025Article
- Association between triglyceride‑glucose index and lumbar bone mineral density among Chinese individuals with osteoporotic fractures: a cross sectional study.Scientific reports · 2025Article
- Multifunctional Nanocarriers for Alzheimer's Disease: Befriending the Barriers.Molecular neurobiology · 2024Review
- Novel insights into D-Pinitol based therapies: a link between tau hyperphosphorylation and insulin resistance.Neural regeneration research · 2024Review
- Anti-Alzheimer Potential of a New (+)-Pinitol Glycoside Isolated fromMetabolites · 2023Article
- Changes in the Carbohydrate Profile in Common Buckwheat (Metabolites · 2023Article
- Current Insights on the Use of Insulin and the Potential Use of Insulin Mimetics in Targeting Insulin Signalling in Alzheimer's Disease.International journal of molecular sciences · 2022Review
- d-Pinitol promotes tau dephosphorylation through a cyclin-dependent kinase 5 regulation mechanism: A new potential approach for tauopathies?British journal of pharmacology · 2022Article
- Review
- Synergistic Neuroprotective Effects of a Natural Product Mixture against AD Hallmarks and Cognitive Decline inNutrients · 2021Article
- A Negative Energy Balance Is Associated with Metabolic Dysfunctions in the Hypothalamus of a Humanized Preclinical Model of Alzheimer's Disease, the 5XFAD Mouse.International journal of molecular sciences · 2021Article
- Role of Inositols and Inositol Phosphates in Energy Metabolism.Molecules (Basel, Switzerland) · 2020Review
- The Biomedical Uses of Inositols: A Nutraceutical Approach to Metabolic Dysfunction in Aging and Neurodegenerative Diseases.Biomedicines · 2020Review
- The Effects of Alpha-Linolenic Acid on the Secretory Activity of Astrocytes andOxidative medicine and cellular longevity · 2020Article
- Acute exercise and brain BACE1 protein content: a time course study.Physiological reports · 2019Article
- Nanoparticle-conjugated nutraceuticals exert prospectively palliative of amyloid aggregation.International journal of nanomedicine · 2018Review
- Filling the void: a role for exercise-induced BDNF and brain amyloid precursor protein processing.American journal of physiology. Regulatory, integrative and comparative physiology · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is a progressive dementia that correlates highly with synapse loss. This loss appears due to the synaptic accumulation of toxic Aβ oligomers (ADDLs), which damages synapse structure and function. Although it has been reported that oligomer binding and toxicity can be prevented by stimulation of neuronal insulin signaling with PPARγ agonists, these agonists have problematic side effects. We therefore investigated the therapeutic potential of chiro-inositols, insulin-sensitizing compounds safe for human consumption. Chiro-inositols have been studied extensively for treatment of diseases associated with peripheral insulin resistance, but their insulin mimetic function in memory-relevant central nervous system (CNS) cells is unknown. Here we demonstrate that mature cultures of hippocampal neurons respond to d-chiro-inositol (DCI), pinitol (3-O-methyl DCI), and the inositol glycan INS-2 (pinitol β-1-4 galactosamine) with increased phosphorylation in key upstream components in the insulin-signaling pathway (insulin receptor, insulin receptor substrate-1, and Akt). Consistent with insulin stimulation, DCI treatment promotes rapid withdrawal of dendritic insulin receptors. With respect to neuroprotection, DCI greatly enhances the ability of insulin to prevent ADDL-induced synapse damage (EC(50) of 90 nM). The mechanism comprises inhibition of oligomer binding at synapses and requires insulin/IGF signaling. DCI showed no effects on Aβ oligomerization. We propose that inositol glycans and DCI, a compound already established as safe for human consumption, have potential as AD therapeutics by protecting CNS synapses against Aβ oligomers through their insulin mimetic activity.
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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 OpenQuestion graph.