Defective lipid metabolism in neurodegeneration with brain iron accumulation (NBIA) syndromes: not only a matter of iron

J Inherit Metab Dis. 2015 Jan;38(1):123-36. doi: 10.1007/s10545-014-9770-z. Epub 2014 Oct 10.

Abstract

Neurodegeneration with brain iron accumulation (NBIA) is a group of devastating and life threatening rare diseases. Adult and early-onset NBIA syndromes are inherited as X-chromosomal, autosomal dominant or recessive traits and several genes have been identified as responsible for these disorders. Among the identified disease genes, only two code for proteins directly involved in iron metabolism while the remaining NBIA genes encode proteins with a wide variety of functions ranging from fatty acid metabolism and autophagy to still unknown activities. It is becoming increasingly evident that many neurodegenerative diseases are associated with metabolic dysfunction that often involves altered lipid metabolism. This is not surprising since neurons have a peculiar and heterogeneous lipid composition critical for the development and correct functioning of the nervous system. This review will focus on specific NBIA forms, namely PKAN, CoPAN, PLAN, FAHN and MPAN, which display an interesting link between neurodegeneration and alteration of phospholipids and sphingolipids metabolism, mitochondrial morphology and membrane remodelling.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism*
  • Fatty Acids / metabolism
  • Humans
  • Iron / chemistry*
  • Iron Metabolism Disorders / genetics
  • Iron Metabolism Disorders / metabolism*
  • Lipid Metabolism*
  • Mitochondria / metabolism
  • Mixed Function Oxygenases / metabolism
  • Neuroaxonal Dystrophies / genetics
  • Neuroaxonal Dystrophies / metabolism*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Pantothenate Kinase-Associated Neurodegeneration / genetics
  • Pantothenate Kinase-Associated Neurodegeneration / metabolism
  • Phospholipids / metabolism
  • Sphingolipids / metabolism
  • Syndrome

Substances

  • Fatty Acids
  • Phospholipids
  • Sphingolipids
  • Iron
  • Mixed Function Oxygenases

Supplementary concepts

  • Neurodegeneration with brain iron accumulation (NBIA)