Phenolic compounds prevent amyloid β-protein oligomerization and synaptic dysfunction by site-specific binding

Topic: Brain proteins, microglia and lab models

Cerebral deposition of amyloid β protein (Aβ) is an invariant feature of Alzheimer disease (AD), and epidemiological evidence suggests that moderate consumption of foods enriched with phenolic compounds reduce the incidence of AD. We reported previously that the phenolic compounds myricetin (Myr) and rosmarinic acid (RA) inhibited Aβ aggregation in vitro and in vivo. To elucidate a mechanistic basis for these results, we analyzed the effects of five phenolic compounds in the Aβ aggregation process and in oligomer-induced synaptic toxicities. We now report that the phenolic compounds blocked Aβ oligomerization, and Myr promoted significant NMR chemical shift changes of monomeric Aβ. Both Myr and RA reduced cellular toxicity and synaptic dysfunction of the Aβ oligomers. These results suggest that Myr and RA may play key roles in blocking the toxicity and early assembly processes associated with Aβ through different binding.

Key findings

• Cerebral deposition of amyloid β protein (Aβ) is an invariant feature of Alzheimer disease (AD), and epidemiological evidence suggests that moderate consumption of foods enriched with phenolic compounds reduce the incidence of AD.
• To elucidate a mechanistic basis for these results, we analyzed the effects of five phenolic compounds in the Aβ aggregation process and in oligomer-induced synaptic toxicities.
• We now report that the phenolic compounds blocked Aβ oligomerization, and Myr promoted significant NMR chemical shift changes of monomeric Aβ.
• These results suggest that Myr and RA may play key roles in blocking the toxicity and early assembly processes associated with Aβ through different binding.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1074/jbc.m111.325456
• PubMed: 22393064
• Original source →

Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.

@article{ono2012-22393064,
  author  = {Ono, K. and Li, L. and Takamura, Y. and Yoshiike, Y. and Zhu, L. and Han, F. and Mao, X. and Ikeda, T. and others},
  title   = {{Phenolic compounds prevent amyloid β-protein oligomerization and synaptic dysfunction by site-specific binding}},
  journal = {The Journal of biological chemistry},
  year    = {2012},
  doi     = {10.1074/jbc.m111.325456},
  pmid    = {22393064},
  url     = {https://doi.org/10.1074/jbc.m111.325456}
}

Related studies in Disease mechanisms

• Role of intestinal microbiota in the generation of polyphenol-derived phenolic acid mediated attenuation of Alzheimer's disease β-amyloid oligomerization Molecular nutrition & food research · 2015-04-27 · usefulness score 36/100
• Transient cerebral ischemia induces site-specific hyperphosphorylation of tau protein Brain research · 2004-10-01 · usefulness score 36/100
• Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity Cold Spring Harbor perspectives in medicine · 2017-05-01 · usefulness score 38/100
• Targeting synaptic dysfunction in Alzheimer's disease by administering a specific nutrient combination Journal of Alzheimer's disease : JAD · 2014 · usefulness score 38/100
• Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016-01-01 · usefulness score 36/100
• CCDC50 mediates the clearance of protein aggregates to prevent cellular proteotoxicity Autophagy · 2024-07-30 · usefulness score 43/100

Similar studies

• Orally available compound prevents deficits in memory caused by the Alzheimer amyloid-beta oligomers 2006 · Disease mechanisms
• Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide 2007 · Disease mechanisms
• Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo 2002 · Disease mechanisms
• Amyloid β oligomers in Alzheimer's disease pathogenesis, treatment, and diagnosis 2015 · Getting a diagnosis
• Amyloid-β oligomerization in Alzheimer dementia versus high-pathology controls 2013 · Risk genes beyond APOE
• Soluble oligomers of amyloid-β peptide disrupt membrane trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor contributing to early synapse dysfunction 2011 · Risk genes beyond APOE

More on Disease mechanisms

• A review that covers this ground Synaptic dysfunction and septin protein family members in neurodegenerative diseases Molecular neurodegeneration · 2015-04-03 · usefulness score 38/100
• Newest in this subject Aβ42 oligomers disrupt calcium homeostasis via Piezo1 and induce neurotoxicity in differentiated SH-SY5Y cells Research Square · 2026-10-29 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject Neuronal Hyperactivity Induces Tau Phosphorylation Selectively in Excitatory Pyramidal Neurons Which Contributes to GluA2 Regulation bioRxiv · 2026-10-28 · Preprint — not yet peer-reviewed · usefulness score 16/100

See all studies in Disease mechanisms →