Starting at the beginning: endoplasmic reticulum proteostasis and systemic amyloid disease

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Updated: Dec 21, 2025

Rapid Generation of Amyloid from Native Proteins In vitro
05:48

Rapid Generation of Amyloid from Native Proteins In vitro

Published on: December 5, 2013

6.4K

Isabelle C Romine1, R Luke Wiseman1

  • 1Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, U.S.A.

The Biochemical Journal
|May 16, 2020
PubMed

Insights

Systemic amyloid diseases involve toxic protein aggregation. Targeting endoplasmic reticulum (ER) proteostasis in protein-producing cells, like the liver, offers a novel therapeutic strategy to reduce amyloid formation and associated toxicity.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pathology

Background:

  • Systemic amyloid diseases feature amyloidogenic protein deposition in peripheral tissues.
  • Traditionally, focus has been on target tissue pathology, overlooking protein synthesis sites.
  • Emerging evidence implicates endoplasmic reticulum (ER) proteostasis in disease pathogenesis.

Purpose of the Study:

  • To explore the pathological role of ER proteostasis in systemic amyloid diseases.
  • To investigate how ER proteostasis regulation impacts extracellular amyloid aggregation.
  • To discuss therapeutic strategies targeting ER proteostasis for amyloid disease treatment.

Main Methods:

  • Review of existing literature on ER proteostasis and systemic amyloid diseases.
  • Analysis of the mechanisms linking ER function to amyloidogenic protein secretion and aggregation.
  • Discussion of potential therapeutic interventions.

Main Results:

  • ER proteostasis pathways significantly influence the pathogenesis of systemic amyloid diseases.
  • Dysregulation of ER proteostasis promotes toxic extracellular aggregation of amyloidogenic proteins.
  • Targeting ER proteostasis can reduce amyloidogenic protein secretion and aggregation.

Conclusions:

  • ER proteostasis is a critical factor in systemic amyloid disease development.
  • Therapeutic strategies aimed at modulating ER proteostasis hold promise for treating these debilitating conditions.
  • Interventions targeting the liver's ER proteostasis could mitigate peripheral amyloid toxicity.
Keywords:
ER proteostasisamyloidogenic proteinsunfolded protein response

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