OPA1: How much do we know to approach therapy?

Pharmacol Res. 2018 May:131:199-210. doi: 10.1016/j.phrs.2018.02.018. Epub 2018 Feb 15.

Abstract

OPA1 is a GTPase that controls several functions, such as mitochondrial dynamics and energetics, mtDNA maintenance and cristae integrity. In the last years, there have been described other cellular pathways and mechanisms involving OPA1 directly or through its interaction. All this new information, by implementing our knowledge on OPA1 is instrumental to elucidating the pathogenic mechanisms of OPA1 mutations. Indeed, these are associated with dominant optic atrophy (DOA), one of the most common inherited optic neuropathies, and with an increasing number of heterogeneous neurodegenerative disorders. In this review, we overview all recent findings on OPA1 protein functions, on its dysfunction and related clinical phenotypes, focusing on the current therapeutic options and future perspectives to treat DOA and the other associated neurological disorders due to OPA1 mutations.

Keywords: DOA therapy; Dominant optic atrophy; Mitochondria dynamics; OPA1 mutations.

Publication types

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

MeSH terms

  • Animals
  • DNA, Mitochondrial / genetics
  • DNA, Mitochondrial / metabolism
  • GTP Phosphohydrolases / genetics*
  • GTP Phosphohydrolases / metabolism
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Mitochondrial Dynamics
  • Mutation*
  • Optic Atrophy, Autosomal Dominant / genetics*
  • Optic Atrophy, Autosomal Dominant / metabolism
  • Optic Atrophy, Autosomal Dominant / pathology
  • Optic Atrophy, Autosomal Dominant / therapy
  • Phenotype

Substances

  • DNA, Mitochondrial
  • GTP Phosphohydrolases
  • OPA1 protein, human