Assessments of the Effect of Neurokinin B on Toxic Aβ Aggregates in Alzheimer's Disease with the Molecular Mechanisms' Action

Olga Press-Sandler, Yifat Miller

Research output: Contribution to journalArticlepeer-review

Abstract

Clinical trials of past and current treatments for Alzheimer's disease (AD) patients on the market suffer from the dual drawbacks of a lack of efficacy and side effects. Neuropeptides have been highlighted by their potential to protect cells against AD and can reverse the toxic effect induced by Aβ in cultured neurons. One of the neuropeptides that has insufficient attention in the literature as a potential treatment for prevention of the progression of AD is neurokinin B (NKB). There are critical and unresolved questions concerning the activation, and the molecular mechanisms underlying NKB effect on prevention of Aβ aggregation remain unknown. The current work identifies for the first time the specific interactions that contribute to the inhibition and prevention of initial seeding of polymorphic early-stage dimers. Three main conclusions are observed in this work. First, NKB inhibits formation of polymorphic early-stage fibrillar Aβ dimers. The efficiency of the inhibition depends on the concentration of NKB (i.e., NKB:Aβ ratio). Second, NKB has an excellent effect of preventing the formation of initial seeding of early-stage nonfibrillar Aβ dimers. Third, NKB peptides may self-assemble to form cross-α fibril-like structure during the inhibition activity of the polymorphic early-stage fibrillar Aβ dimers but not during the prevention activity of early-stage nonfibrillar Aβ dimers. The work provides crucial information for future experimental studies to approve the functional effect of NKB on inhibition and prevention of Aβ polymorphic early-stage oligomers.

Original languageAmerican English
Pages (from-to)3418-3429
Number of pages12
JournalACS Chemical Neuroscience
Volume11
Issue number20
DOIs
StatePublished - 21 Oct 2020

Keywords

  • Aβ oligomers
  • aromatic interactions
  • inhibitors
  • neurodegenerative diseases
  • neuropeptides
  • self-assembly

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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