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

• Published in: Mammalian genome Vol. 28; no. 9-10; pp. 395 - 406
• Main Authors: Finelli, Mattéa J., Oliver, Peter L.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2017; Springer Nature B.V
• Subjects: Animal Genetics and Genomics; Animals; Apoptosis; Biomedical and Life Sciences; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Biology; Cell death; Drug Discovery; Epilepsy; GTPase-Activating Proteins; Hearing loss; Human Genetics; Humans; Life Sciences; Membrane Proteins; Mitochondrial Proteins; Nerve Tissue Proteins; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - physiopathology; Neurological diseases; Neuroprotection; Nuclear Receptor Coactivators - genetics; Nuclear Receptor Coactivators - metabolism; Oxidative stress; Oxidative Stress - genetics; Protein Domains; Proteins; Proteins - genetics; Proteins - metabolism; Reactive Oxygen Species - metabolism; Redox properties; Nuclear Receptor Coactivator (NCOA7); ADP-ribosylation Factor (ARF6); Falace; hSOD1G93A Mice; TBC1 Domain Family Member (TBC1D24)
• ISSN: 0938-8990; 1432-1777
• DOI: 10.1007/s00335-017-9706-7

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.