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Related Concept Videos

Alzheimer's Disease: Treatment01:22

Alzheimer's Disease: Treatment

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Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
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Selecting Multitarget Peptides for Alzheimer's Disease.

Anne Kasus-Jacobi1,2, Jennifer L Washburn1, Riley B Laurence1

  • 1Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA.

Biomolecules
|October 27, 2022
PubMed
Summary

Researchers identified a novel peptide targeting key Alzheimer's disease pathways. This multitarget peptide shows promise in combating neuroinflammation and neurodegeneration, potentially slowing cognitive decline.

Keywords:
Alzheimer’s diseaseS100 calcium-binding protein A9Toll-like receptor 4amyloid betacathepsin Gmultitarget drugneurodegenerationneuroinflammationneutrophilreceptor for advanced glycation end-products

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disorder characterized by progressive cognitive decline.
  • Current therapeutic strategies often target single pathways, limiting efficacy against the multifaceted nature of AD.
  • Multitarget drug development offers a promising approach to address the complex pathogenesis of Alzheimer's disease.

Purpose of the Study:

  • To identify and select a multitarget peptide candidate for Alzheimer's disease treatment.
  • To evaluate peptide variants derived from cathepsin G for their potential to inhibit key AD-related molecular targets.
  • To find a lead peptide with inherent multitarget activity for impacting cognitive decline.

Main Methods:

  • Screened eight peptide candidates derived from cathepsin G.
  • Assessed inhibition and reversion of amyloid beta (Aβ) oligomers using ELISA.
  • Quantified peptide binding to receptor for advanced glycation end-products (RAGE), Toll-like receptor 4 (TLR4), and S100A9 via ELISA.
  • Evaluated protection against Aβ oligomer-induced neuronal cell death using trypan blue assay.
  • Measured inhibition of TLR4 activation by S100A9 in a reporter cell line.

Main Results:

  • A 27-mer lead peptide was selected, demonstrating efficacy across all four screening criteria.
  • The selected peptide effectively inhibited and reversed amyloid beta oligomers.
  • The peptide exhibited direct binding to RAGE, TLR4, and S100A9.
  • It provided protection against Aβ oligomer-induced neuronal cell death and inhibited TLR4 activation.

Conclusions:

  • A novel 27-mer peptide was identified as a promising multitarget therapeutic candidate for Alzheimer's disease.
  • This lead peptide possesses inherent multitarget activity, addressing both neuroinflammation and neurodegeneration.
  • The peptide is expected to significantly impact cognitive decline in Alzheimer's disease models by targeting critical pathological pathways.