Autophagy receptor defects and ALS-FTLD

Mol Cell Neurosci. 2015 May;66(Pt A):43-52. doi: 10.1016/j.mcn.2015.01.002. Epub 2015 Feb 12.


Various pathophysiological mechanisms have been implicated in the ALS-FTLD clinicopathological spectrum of neurodegenerative disorders. Here we focus on the role of autophagy, an intracellular catabolic pathway, in these conditions. Growing evidence suggests that the autophagic process can be disturbed in ALS-FTLD, including by genetic mutations affecting autophagy receptor proteins (ubiquilin-2, optineurin, SQSTM1/p62) and regulators (VCP). Such mutations may impair clearance of autophagy substrates with pathological consequences. Recent studies have also uncovered a direct connection between autophagy and RNA processing, supporting an integrated model connecting several ALS-FTLD associated gene products. This article is part of a Special Issue entitled 'Neuronal Protein'.

Keywords: ALS; Autophagy; FTLD; Optineurin; SQSTM1/p62; Stress granules; Ubiquilin; VCP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Animals
  • Autophagy / physiology*
  • Frontotemporal Lobar Degeneration / physiopathology*
  • Humans
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Signal Transduction / physiology*


  • Nerve Tissue Proteins