Assessing Autophagic Activity and Aggregate Formation of Mutant Huntingtin in Mammalian Cells

Methods Mol Biol. 2018:1780:17-29. doi: 10.1007/978-1-4939-7825-0_2.

Abstract

The accumulation of mutant aggregate-prone proteins is a hallmark of the majority of neurodegenerative disorders, including Alzheimer's, Parkinson's, and Huntington's diseases. Autophagy, a cytosolic bulk degradation system, is the major clearance pathway for several aggregate-prone proteins, such as mutant huntingtin. The autophagosome-associated protein LC3-II is a specific marker of autophagic flux within cells, whereas aggregate formation of mutant huntingtin represents a good readout for studying autophagy modulation. Here we describe the method of assessing autophagic flux using LC3-II western blotting and substrate clearance by expressing the N-terminal fragment of huntingtin (htt exon 1) containing an expanded polyglutamine tract in mammalian cells.

Keywords: Autophagic flux; Autophagy; Bafilomycin A1; Huntingtin aggregates; LC3-II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / genetics*
  • Blotting, Western / instrumentation
  • Blotting, Western / methods*
  • Exons / genetics
  • HeLa Cells
  • Humans
  • Huntingtin Protein / genetics
  • Huntingtin Protein / metabolism*
  • Microtubule-Associated Proteins / analysis*
  • Microtubule-Associated Proteins / metabolism
  • Mutation
  • Neurodegenerative Diseases / diagnosis*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / pathology
  • Protein Aggregation, Pathological / diagnosis*
  • Protein Aggregation, Pathological / genetics
  • Protein Aggregation, Pathological / pathology
  • Proteolysis

Substances

  • HTT protein, human
  • Huntingtin Protein
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins