Biochemical characterization of a neuroserpin variant associated with hereditary dementia

M. Yazaki, J. J. Liepnieks, J. R. Murrell, M. Takao, B. Guenther, P. Piccardo, Martin Farlow, Bernardino Ghetti, Merrill Benson

Research output: Contribution to journalArticle

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Abstract

Neuroserpin isolated from inclusion bodies in the brain of a patient with a neurodegenerative disease was characterized biochemically. The protein consisted of residues 20 to 410 of the neuroserpin precursor deduced from its cDNA sequence indicating the entire molecule was deposited. A minor amount started with residue 19 of the precursor, and the carboxyl terminus was heterogeneous ending at residues 405, 407, 409, and 410. Arg was present at position 52. No normal Ser52 was found indicating that only mutant neuroserpin was present in the inclusion bodies. The three potential Asn glycosylation sites all contained carbohydrate. DNA sequence analysis of exons 2 to 9 of the neuroserpin gene in the proband showed the published normal neuroserpin sequence except for the presence of both adenine and cytosine at the first position of codon 52, that indicates heterozygosity for both the normal Ser(AGT) and variant Arg(CGT) at this position in the expressed protein. Restriction fragment length polymorphism analysis of a polymerase chain reaction product from exon 2 revealed the propositus and his affected sibling both were heterozygous for the mutation whereas 100 unaffected controls were negative. Chemical characterization of the variant neuroserpin will significantly enhance the understanding of this protein in both normal physiology and neurodegenerative diseases.

Original languageEnglish
Pages (from-to)227-233
Number of pages7
JournalAmerican Journal of Pathology
Volume158
Issue number1
StatePublished - 2001

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Dementia
Inclusion Bodies
Neurodegenerative Diseases
Exons
Proteins
Cytosine
Adenine
DNA Sequence Analysis
Glycosylation
Codon
Restriction Fragment Length Polymorphisms
neuroserpin
Siblings
Complementary DNA
Carbohydrates
Polymerase Chain Reaction
Mutation
Brain
Genes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Yazaki, M., Liepnieks, J. J., Murrell, J. R., Takao, M., Guenther, B., Piccardo, P., ... Benson, M. (2001). Biochemical characterization of a neuroserpin variant associated with hereditary dementia. American Journal of Pathology, 158(1), 227-233.

Biochemical characterization of a neuroserpin variant associated with hereditary dementia. / Yazaki, M.; Liepnieks, J. J.; Murrell, J. R.; Takao, M.; Guenther, B.; Piccardo, P.; Farlow, Martin; Ghetti, Bernardino; Benson, Merrill.

In: American Journal of Pathology, Vol. 158, No. 1, 2001, p. 227-233.

Research output: Contribution to journalArticle

Yazaki, M, Liepnieks, JJ, Murrell, JR, Takao, M, Guenther, B, Piccardo, P, Farlow, M, Ghetti, B & Benson, M 2001, 'Biochemical characterization of a neuroserpin variant associated with hereditary dementia', American Journal of Pathology, vol. 158, no. 1, pp. 227-233.
Yazaki M, Liepnieks JJ, Murrell JR, Takao M, Guenther B, Piccardo P et al. Biochemical characterization of a neuroserpin variant associated with hereditary dementia. American Journal of Pathology. 2001;158(1):227-233.
Yazaki, M. ; Liepnieks, J. J. ; Murrell, J. R. ; Takao, M. ; Guenther, B. ; Piccardo, P. ; Farlow, Martin ; Ghetti, Bernardino ; Benson, Merrill. / Biochemical characterization of a neuroserpin variant associated with hereditary dementia. In: American Journal of Pathology. 2001 ; Vol. 158, No. 1. pp. 227-233.
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