Intracellular Ferritin Accumulation in Neural and Extraneural Tissue Characterizes A Neurodegenerative Disease Associated with A Mutation in the Ferritin Light Polypeptide Gene

Ruben Vidal, Bernardino Ghetti, M. Takao, C. Brefel-Courbon, E. Uro-Coste, B. S. Glazier, V. Siani, Merrill Benson, P. Calvas, L. Miravalle, O. Rascol, M. B. Delisle

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Abnormal accumulation of ferritin was found to be associated with an autosomal dominant slowly progressing neurodegenerative disease clinically characterized by tremor, cerebellar ataxia, parkinsonism and pyramidal signs, behavioral disturbances, and cognitive decline. These symptoms may appear sequentially over a period of 4 decades. Pathologically, intranuclear and intracytoplasmic bodies were found in glia and subsets of neurons in the central nervous system as well as in extraneural tissue. Biochemical analyses of these bodies isolated from the striatum and cerebellar cortex revealed that ferritin light polypeptide (FTL) and ferritin heavy polypeptide (FTH1) were the main constituents. Molecular genetic studies revealed a 2-bp insertion mutation in exon 4 of the FTL gene. The resulting mutant polypeptide is predicted to have a carboxy terminus that is altered in amino-acid sequence and length. In tissue sections, the bodies were immunolabeled by anti-ferritin and anti-ubiquitin antibodies and were stained by Perls' method for ferric iron. Synthetic peptides homologous to the altered and wild-type carboxy termini were used to raise polyclonal antibodies. These novel antibodies as well as an antibody recognizing FTH1 immunolabeled the bodies. This study of this disorder has provided additional knowledge and insights in the growing area of ferritin-related neurodegeneration.

Original languageEnglish
Pages (from-to)363-380
Number of pages18
JournalJournal of Neuropathology and Experimental Neurology
Volume63
Issue number4
StatePublished - Apr 2004

Fingerprint

Ferritins
Neurodegenerative Diseases
Light
Peptides
Mutation
Genes
Antibodies
Cerebellar Ataxia
Cerebellar Cortex
Insertional Mutagenesis
Parkinsonian Disorders
Tremor
Ubiquitin
Neuroglia
Molecular Biology
Anti-Idiotypic Antibodies
Amino Acid Sequence
Exons
Iron
Central Nervous System

Keywords

  • Ataxia
  • Dementia
  • Extrapyramidal signs
  • Ferritin
  • Iron
  • Neurodegeneration
  • Tremor

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Intracellular Ferritin Accumulation in Neural and Extraneural Tissue Characterizes A Neurodegenerative Disease Associated with A Mutation in the Ferritin Light Polypeptide Gene. / Vidal, Ruben; Ghetti, Bernardino; Takao, M.; Brefel-Courbon, C.; Uro-Coste, E.; Glazier, B. S.; Siani, V.; Benson, Merrill; Calvas, P.; Miravalle, L.; Rascol, O.; Delisle, M. B.

In: Journal of Neuropathology and Experimental Neurology, Vol. 63, No. 4, 04.2004, p. 363-380.

Research output: Contribution to journalArticle

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