ADAM10 in Alzheimer's disease: Pharmacological modulation by natural compounds and its role as a peripheral marker

Biomed Pharmacother. 2019 May:113:108661. doi: 10.1016/j.biopha.2019.108661. Epub 2019 Mar 2.

Abstract

Alzheimer's disease (AD) represents a global burden in the economics of healthcare systems. Amyloid-β (Aβ) peptides are formed by amyloid-β precursor protein (AβPP) cleavage, which can be processed by two pathways. The cleavage by the α-secretase A Disintegrin And Metalloprotease 10 (ADAM10) releases the soluble portion (sAβPPα) and prevents senile plaques. This pathway remains largely unknown and ignored, mainly regarding pharmacological approaches that may act via different signaling cascades and thus stimulate non-amyloidogenic cleavage through ADAM10. This review emphasizes the effects of natural compounds on ADAM10 modulation, which eventuates in a neuroprotective mechanism. Moreover, ADAM10 as an AD biomarker is revised. New treatments and preventive interventions targeting ADAM10 regulation for AD are necessary, considering the wide variety of ADAM10 substrates.

Keywords: ADAM10; Alzheimer’s disease; Natural compounds; Pharmaceutical; α-Secretase.

Publication types

  • Review

MeSH terms

  • ADAM10 Protein / metabolism*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / prevention & control*
  • Amyloid Precursor Protein Secretases / metabolism*
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / metabolism
  • Biomarkers / metabolism
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Ginkgo biloba
  • Humans
  • Membrane Proteins / metabolism*
  • Neuroprotective Agents / pharmacology*
  • Plant Extracts / pharmacology*

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Biomarkers
  • Membrane Proteins
  • Neuroprotective Agents
  • Plant Extracts
  • Ginkgo biloba extract
  • Catechin
  • epigallocatechin gallate
  • Amyloid Precursor Protein Secretases
  • ADAM10 Protein
  • ADAM10 protein, human