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Assays for the Degradation of Misfolded Proteins in Cells
10:56

Assays for the Degradation of Misfolded Proteins in Cells

Published on: August 28, 2016

Molecular pathogenesis of protein misfolding diseases: pathological molecular environments versus quality control

Hironobu Naiki1, Yoshitaka Nagai

  • 1Division of Molecular Pathology, Department of Pathological Sciences, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan. naiki@u-fukui.ac.jp

Journal of Biochemistry
|August 1, 2009
PubMed

Insights

Protein misfolding diseases, like neurodegenerative disorders, stem from protein aggregation. Targeting protein misfolding and aggregation offers a promising therapeutic strategy for these conditions.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pathology

Background:

  • Diverse human diseases, including neurodegenerative disorders and amyloidoses, are characterized by protein misfolding and aggregation.
  • These conditions, termed protein misfolding diseases, involve native proteins transitioning to beta-sheet conformations and forming amyloid fibrils.
  • Examples include beta(2)-microglobulin amyloidosis and intracellular polyglutamine neurodegenerative diseases.

Purpose of the Study:

  • To explore the mechanisms of protein misfolding and aggregation in various diseases.
  • To investigate the role of biological molecules and protein quality control systems in these processes.
  • To identify protein misfolding and aggregation as potential therapeutic targets.

Main Methods:

  • Review of existing literature on protein misfolding diseases.
  • Analysis of the roles of extracellular molecules (e.g., glycosaminoglycans, lipids) in beta(2)-microglobulin amyloidosis.
  • Examination of intracellular protein quality control systems (e.g., molecular chaperones, ubiquitin-proteasome system, autophagy-lysosome system) in polyglutamine diseases.

Main Results:

  • Extracellular molecules can catalyze and stabilize beta(2)-microglobulin fibril formation.
  • Intracellular protein quality control systems tightly regulate protein homeostasis and disease progression.
  • Extracellular chaperones can inhibit amyloid fibril formation by binding to misfolded proteins.

Conclusions:

  • Protein misfolding and aggregation are central to a range of debilitating human diseases.
  • Understanding the interplay between proteins, biological molecules, and cellular systems is crucial.
  • Targeting protein misfolding and aggregation pathways presents a viable therapeutic avenue for protein misfolding diseases.

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