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

  • Complex Lipids
  • Published:
Journal of Inherited Metabolic Disease

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

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Abbreviations

2-hFA :

2-hydroxylated fatty acids

2-nFA :

2-non hydroxylated fatty acids

2-OHOA :

2’-hydroxyoleic acidp

AA :

arachidonic acid

ATP :

Adenosine triphosphate

C19orf12 :

chromosome 19 open-reading frame 12 gene

CL :

cardiolipin

CL-ox :

oxidized CL

CNS :

central nervous system

CoA :

coenzyme A

DHA :

docosahexaenoic acid

ENU :

N-ethyl-N-nitrosourea

EPA :

eicosapentaenoic acid

ER :

endoplasmic reticulum

FA :

fatty acids

GalCer :

galactosylceramide

LPC :

lysophosphatidylcholine

MPAN :

mitochondrial membrane protein-associated neurodegeneration

MRI :

magnetic resonance imaging

PC :

phosphatidylcholine

PE :

phosphatidylethanolamine

PKAN :

PANK-associated neurodegeneration with brain iron accumulation

PL :

phospholipids

PLAN :

PLA2G6-associated neurodegeneration with brain iron accumulation

PNS :

peripheral nervous system

PPARs :

peroxisome proliferator-activated receptors

PS :

phosphatidylserine

PUFA :

poly-unsaturated fatty acids

ROS :

reactive oxygen species

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Acknowledgments

The support of Telethon GGP11088 and TIRCON project of the European Commission’s Seventh Framework Programme (FP7/2007-2013, HEALTH-F2-2011, grant agreement No. 277984) to VT are gratefully acknowledged. MA is supported by the Mitochondrial European Educational

Training, MEET, ITN MARIE CURIE PEOPLE (grant agreement No. 317433).

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None.

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Authors and Affiliations

  1. Unit of Molecular Neurogenetics - Pierfranco and Luisa Mariani Centre for the Study of Mitochondrial Disorders in Children, Foundation IRCCS Neurological Institute “Carlo Besta”, Via Temolo 4, 20126, Milan, Italy

    Cristina Colombelli, Manar Aoun & Valeria Tiranti

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  1. Cristina Colombelli
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  2. Manar Aoun
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  3. Valeria Tiranti
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Correspondence to Valeria Tiranti.

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Communicated by: Jean-Marie Saudubray

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Colombelli, C., Aoun, M. & Tiranti, V. Defective lipid metabolism in neurodegeneration with brain iron accumulation (NBIA) syndromes: not only a matter of iron. J Inherit Metab Dis 38, 123–136 (2015). https://doi.org/10.1007/s10545-014-9770-z

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  • DOI: https://doi.org/10.1007/s10545-014-9770-z

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