Proteomic analysis of lymphoblastoid cells from Nasu-Hakola patients: a step forward in our understanding of this neurodegenerative disorder

Serena Giuliano; Anna Maria Agresta; Antonella De Palma; Simona Viglio; Pierluigi Mauri; Marco Fumagalli; Paolo Iadarola; Lorenza Montalbetti; Roberta Salvini; Anna Bardoni

doi:10.1371/journal.pone.0110073

Proteomic analysis of lymphoblastoid cells from Nasu-Hakola patients: a step forward in our understanding of this neurodegenerative disorder

PLoS One. 2014 Dec 3;9(12):e110073. doi: 10.1371/journal.pone.0110073. eCollection 2014.

Affiliations

¹ Department of Molecular Medicine, Biochemistry Unit, University of Pavia, Pavia, Italy; Laboratoire d'excellence-Ion channel science and therapeutics, UMR, CNRS, Nice, France.
² Institute for Biochemical Technologies, Proteomics and Metabolomics Unit, National Research Council, Segrate (Milano), Italy.
³ Department of Molecular Medicine, Biochemistry Unit, University of Pavia, Pavia, Italy.
⁴ Department of Biology and Biotechnologies, Biochemistry Unit, University of Pavia, Pavia, Italy.
⁵ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.

Abstract

Nasu-Hakola disease (NHD) is a recessively inherited rare disorder characterized by a combination of neuropsychiatric and bone symptoms which, while being unique to this disease, do not provide a rationale for the unambiguous identification of patients. These individuals, in fact, are likely to go unrecognized either because they are considered to be affected by other kinds of dementia or by fibrous dysplasia of bone. Given that dementia in NHD has much in common with Alzheimer's disease and other neurodegenerative disorders, it cannot be expected to achieve the differential diagnosis of this disease without performing a genetic analysis. Under this scenario, the availability of protein biomarkers would indeed provide a novel context to facilitate interpretation of symptoms and to make the precise identification of this disease possible. The work here reported was designed to generate, for the first time, protein profiles of lymphoblastoid cells from NHD patients. Two-dimensional electrophoresis (2-DE) and nano liquid chromatography-tandem mass spectrometry (nLC-MS/MS) have been applied to all components of an Italian family (seven subjects) and to five healthy subjects included as controls. Comparative analyses revealed differences in the expression profile of 21 proteins involved in glucose metabolism and information pathways as well as in stress responses.

Publication types

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

MeSH terms

Adult
Aged
Case-Control Studies
Chromatography, Liquid
Electrophoresis, Gel, Two-Dimensional
Female
Gene Expression Regulation
Humans
Italy
Lipodystrophy / genetics*
Lipodystrophy / metabolism
Lipodystrophy / pathology*
Lymphocytes / metabolism*
Male
Membrane Glycoproteins / genetics*
Middle Aged
Osteochondrodysplasias / genetics*
Osteochondrodysplasias / metabolism
Osteochondrodysplasias / pathology*
Pedigree
Proteins / metabolism*
Proteomics / methods*
Receptors, Immunologic / genetics*
Subacute Sclerosing Panencephalitis / genetics*
Subacute Sclerosing Panencephalitis / metabolism
Subacute Sclerosing Panencephalitis / pathology*
Tandem Mass Spectrometry
Young Adult

Substances

Membrane Glycoproteins
Proteins
Receptors, Immunologic
TREM2 protein, human

Supplementary concepts

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy

Grants and funding

This study was supported by the Italian Ministry of University and Research for the PON project (01_01426, AMA, PM) and by CARE-G project financed by Regione Lombardia (ADP, PM). The authors are deeply grateful to Laura Fossati Onlus (Montesegale, Pavia, Italy) for the generous financial support provided to the Biochemistry Unit of the Department of Molecular Medicine for the realization of this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.