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Chaperone-mediated autophagy in aging and neurodegeneration: lessons from alpha-synuclein

Urmi Bandyopadhyay1, Urmi Bandhyopadhyay, Ana Maria Cuervo

  • 1Department of Anatomy and Structural Biology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Experimental Gerontology
|July 25, 2006
PubMed

Insights

Misfolded proteins cause cellular damage and neurodegenerative diseases. This review explores how impaired autophagy contributes to these disorders, using Parkinson disease as a key example.

Area of Science:

  • Cellular Biology
  • Neuroscience
  • Biochemistry

Background:

  • Misfolded or conformationally altered proteins accumulate intracellularly due to genetic mutations or post-translational modifications.
  • These abnormal proteins can form toxic oligomers, leading to cellular dysfunction and death.
  • Dysregulation of cellular surveillance systems, responsible for protein repair or clearance, underlies many neurodegenerative disorders.

Purpose of the Study:

  • To review protein conformational disorders and the role of intracellular proteolytic systems, particularly autophagy, in their progression.
  • To examine the cellular stages of Parkinson disease as a model protein conformational disorder.
  • To discuss the impact of aggravating factors like oxidative stress and aging on autophagy's ability to manage altered proteins.

Main Methods:

  • Literature review focusing on protein conformational disorders and autophagy.
  • Analysis of cellular mechanisms in Parkinson disease.
  • Discussion of the interplay between aging, oxidative stress, and autophagic function.

Main Results:

  • Altered protein conformations are implicated in cellular death and neurodegeneration.
  • Impaired autophagy is a key factor in the pathogenesis of protein conformational disorders.
  • Parkinson disease exemplifies the cellular consequences of protein misfolding and autophagic dysfunction.
  • Aging and oxidative stress exacerbate autophagic system dysfunction, hindering clearance of abnormal proteins.

Conclusions:

  • Autophagy plays a critical role in managing intracellular misfolded proteins and preventing neurodegeneration.
  • Dysfunction in autophagic pathways contributes significantly to the development and progression of protein conformational disorders.
  • Understanding the impact of aging and oxidative stress on autophagy is crucial for developing therapeutic strategies for neurodegenerative diseases.

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