Neurodegeneration with brain iron accumulation: Update on pathogenic mechanisms

Sonia Levi, Dario Finazzi

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Perturbation of iron distribution is observed in many neurodegenerative disorders, including Alzheimer's and Parkinson's disease, but the comprehension of the metal role in the development and progression of such disorders is still very limited. The combination of more powerful brain imaging techniques and faster genomic DNA sequencing procedures has allowed the description of a set of genetic disorders characterized by a constant and often early accumulation of iron in specific brain regions and the identification of the associated genes; these disorders are now collectively included in the category of neurodegeneration with brain iron accumulation (NBIA). So far 10 different genetic forms have been described but this number is likely to increase in short time. Two forms are linked to mutations in genes directly involved in iron metabolism: neuroferritinopathy, associated to mutations in the FTL gene and aceruloplasminemia, where the ceruloplasmin gene product is defective. In the other forms the connection with iron metabolism is not evident at all and the genetic data let infer the involvement of other pathways: Pank2, Pla2G6, C19orf12, COASY, and FA2H genes seem to be related to lipid metabolism and to mitochondria functioning, WDR45 and ATP13A2 genes are implicated in lysosomal and autophagosome activity, while the C2orf37 gene encodes a nucleolar protein of unknown function. There is much hope in the scientific community that the study of the NBIA forms may provide important insight as to the link between brain iron metabolism and neurodegenerative mechanisms and eventually pave the way for new therapeutic avenues also for the more common neurodegenerative disorders. In this work, we will review the most recent findings in the molecular mechanisms underlining the most common forms of NBIA and analyze their possible link with brain iron metabolism.

Original languageEnglish
Article number99
JournalFrontiers in Pharmacology
Volume5 MAY
DOIs
Publication statusPublished - 2014

Fingerprint

Iron
Genes
Neurodegenerative Diseases
Brain
Mutation
Inborn Genetic Diseases
Ceruloplasmin
Nuclear Proteins
Neurodegeneration with brain iron accumulation (NBIA)
DNA Sequence Analysis
Lipid Metabolism
Neuroimaging
Parkinson Disease
Alzheimer Disease
Mitochondria
Metals
Therapeutics

Keywords

  • Brain
  • Iron
  • NBIA disorders
  • Neurodegeneration
  • Oxidative stress
  • Pathogenesis

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Neurodegeneration with brain iron accumulation : Update on pathogenic mechanisms. / Levi, Sonia; Finazzi, Dario.

In: Frontiers in Pharmacology, Vol. 5 MAY, 99, 2014.

Research output: Contribution to journalArticle

@article{0b8b5924ce4d421cb240fc293f2330ff,
title = "Neurodegeneration with brain iron accumulation: Update on pathogenic mechanisms",
abstract = "Perturbation of iron distribution is observed in many neurodegenerative disorders, including Alzheimer's and Parkinson's disease, but the comprehension of the metal role in the development and progression of such disorders is still very limited. The combination of more powerful brain imaging techniques and faster genomic DNA sequencing procedures has allowed the description of a set of genetic disorders characterized by a constant and often early accumulation of iron in specific brain regions and the identification of the associated genes; these disorders are now collectively included in the category of neurodegeneration with brain iron accumulation (NBIA). So far 10 different genetic forms have been described but this number is likely to increase in short time. Two forms are linked to mutations in genes directly involved in iron metabolism: neuroferritinopathy, associated to mutations in the FTL gene and aceruloplasminemia, where the ceruloplasmin gene product is defective. In the other forms the connection with iron metabolism is not evident at all and the genetic data let infer the involvement of other pathways: Pank2, Pla2G6, C19orf12, COASY, and FA2H genes seem to be related to lipid metabolism and to mitochondria functioning, WDR45 and ATP13A2 genes are implicated in lysosomal and autophagosome activity, while the C2orf37 gene encodes a nucleolar protein of unknown function. There is much hope in the scientific community that the study of the NBIA forms may provide important insight as to the link between brain iron metabolism and neurodegenerative mechanisms and eventually pave the way for new therapeutic avenues also for the more common neurodegenerative disorders. In this work, we will review the most recent findings in the molecular mechanisms underlining the most common forms of NBIA and analyze their possible link with brain iron metabolism.",
keywords = "Brain, Iron, NBIA disorders, Neurodegeneration, Oxidative stress, Pathogenesis",
author = "Sonia Levi and Dario Finazzi",
year = "2014",
doi = "10.3389/fphar.2014.00099",
language = "English",
volume = "5 MAY",
journal = "Frontiers in Pharmacology",
issn = "1663-9812",
publisher = "Frontiers Media S.A.",

}

TY - JOUR

T1 - Neurodegeneration with brain iron accumulation

T2 - Update on pathogenic mechanisms

AU - Levi, Sonia

AU - Finazzi, Dario

PY - 2014

Y1 - 2014

N2 - Perturbation of iron distribution is observed in many neurodegenerative disorders, including Alzheimer's and Parkinson's disease, but the comprehension of the metal role in the development and progression of such disorders is still very limited. The combination of more powerful brain imaging techniques and faster genomic DNA sequencing procedures has allowed the description of a set of genetic disorders characterized by a constant and often early accumulation of iron in specific brain regions and the identification of the associated genes; these disorders are now collectively included in the category of neurodegeneration with brain iron accumulation (NBIA). So far 10 different genetic forms have been described but this number is likely to increase in short time. Two forms are linked to mutations in genes directly involved in iron metabolism: neuroferritinopathy, associated to mutations in the FTL gene and aceruloplasminemia, where the ceruloplasmin gene product is defective. In the other forms the connection with iron metabolism is not evident at all and the genetic data let infer the involvement of other pathways: Pank2, Pla2G6, C19orf12, COASY, and FA2H genes seem to be related to lipid metabolism and to mitochondria functioning, WDR45 and ATP13A2 genes are implicated in lysosomal and autophagosome activity, while the C2orf37 gene encodes a nucleolar protein of unknown function. There is much hope in the scientific community that the study of the NBIA forms may provide important insight as to the link between brain iron metabolism and neurodegenerative mechanisms and eventually pave the way for new therapeutic avenues also for the more common neurodegenerative disorders. In this work, we will review the most recent findings in the molecular mechanisms underlining the most common forms of NBIA and analyze their possible link with brain iron metabolism.

AB - Perturbation of iron distribution is observed in many neurodegenerative disorders, including Alzheimer's and Parkinson's disease, but the comprehension of the metal role in the development and progression of such disorders is still very limited. The combination of more powerful brain imaging techniques and faster genomic DNA sequencing procedures has allowed the description of a set of genetic disorders characterized by a constant and often early accumulation of iron in specific brain regions and the identification of the associated genes; these disorders are now collectively included in the category of neurodegeneration with brain iron accumulation (NBIA). So far 10 different genetic forms have been described but this number is likely to increase in short time. Two forms are linked to mutations in genes directly involved in iron metabolism: neuroferritinopathy, associated to mutations in the FTL gene and aceruloplasminemia, where the ceruloplasmin gene product is defective. In the other forms the connection with iron metabolism is not evident at all and the genetic data let infer the involvement of other pathways: Pank2, Pla2G6, C19orf12, COASY, and FA2H genes seem to be related to lipid metabolism and to mitochondria functioning, WDR45 and ATP13A2 genes are implicated in lysosomal and autophagosome activity, while the C2orf37 gene encodes a nucleolar protein of unknown function. There is much hope in the scientific community that the study of the NBIA forms may provide important insight as to the link between brain iron metabolism and neurodegenerative mechanisms and eventually pave the way for new therapeutic avenues also for the more common neurodegenerative disorders. In this work, we will review the most recent findings in the molecular mechanisms underlining the most common forms of NBIA and analyze their possible link with brain iron metabolism.

KW - Brain

KW - Iron

KW - NBIA disorders

KW - Neurodegeneration

KW - Oxidative stress

KW - Pathogenesis

UR - http://www.scopus.com/inward/record.url?scp=84904622975&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904622975&partnerID=8YFLogxK

U2 - 10.3389/fphar.2014.00099

DO - 10.3389/fphar.2014.00099

M3 - Article

AN - SCOPUS:84904622975

VL - 5 MAY

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

SN - 1663-9812

M1 - 99

ER -