TLDc proteins: new players in the oxidative stress response and neurological disease

Mamm Genome. 2017 Oct;28(9-10):395-406. doi: 10.1007/s00335-017-9706-7. Epub 2017 Jul 13.


Oxidative stress (OS) arises from an imbalance in the cellular redox state, which can lead to intracellular damage and ultimately cell death. OS occurs as a result of normal ageing, but it is also implicated as a common etiological factor in neurological disease; thus identifying novel proteins that modulate the OS response may facilitate the design of new therapeutic approaches applicable to many disorders. In this review, we describe the recent progress that has been made using a range of genetic approaches to understand a family of proteins that share the highly conserved TLDc domain. We highlight their shared ability to prevent OS-related cell death and their unique functional characteristics, as well as discussing their potential application as new neuroprotective factors. Furthermore, with an increasing number of pathogenic mutations leading to epilepsy and hearing loss being discovered in the TLDc protein TBC1D24, understanding the function of this family has important implications for a range of inherited neurological diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Drug Discovery
  • GTPase-Activating Proteins
  • Humans
  • Membrane Proteins
  • Mitochondrial Proteins
  • Nerve Tissue Proteins
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / physiopathology
  • Nuclear Receptor Coactivators / genetics
  • Nuclear Receptor Coactivators / metabolism
  • Oxidative Stress / genetics*
  • Protein Domains
  • Proteins / genetics
  • Proteins / metabolism
  • Reactive Oxygen Species / metabolism


  • Carrier Proteins
  • GTPase-Activating Proteins
  • Membrane Proteins
  • Mitochondrial Proteins
  • NCOA7 protein, human
  • Nerve Tissue Proteins
  • Nuclear Receptor Coactivators
  • OXR1 protein, human
  • Proteins
  • Reactive Oxygen Species
  • TBC1D24 protein, human