title: Amyotrophic lateral sclerosis multiprotein biomarkers in peripheral blood mononuclear cells.
abstract: BACKGROUND
  Amyotrophic lateral sclerosis (ALS) is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostic test and therapy. Specific molecular biomarkers are urgently needed to facilitate clinical studies and speed up the development of effective treatments.
  
  
  RESULTS
  We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC), a panel of protein biomarkers that are closely associated with ALS. Validations and a longitudinal study were performed by immunoassays on a selected number of proteins. The same proteins were also measured in PBMC and spinal cord of a G93A SOD1 transgenic rat model. We identified combinations of protein biomarkers that can distinguish, with high discriminatory power, ALS patients from healthy controls (98%), and from patients with neurological disorders that may resemble ALS (91%), between two levels of disease severity (90%), and a number of translational biomarkers, that link responses between human and animal model. We demonstrated that TDP-43, cyclophilin A and ERp57 associate with disease progression in a longitudinal study. Moreover, the protein profile changes detected in peripheral blood mononuclear cells of ALS patients are suggestive of possible intracellular pathogenic mechanisms such as endoplasmic reticulum stress, nitrative stress, disturbances in redox regulation and RNA processing.
  
  
  CONCLUSIONS
  Our results indicate that PBMC multiprotein biomarkers could contribute to determine amyotrophic lateral sclerosis diagnosis, differential diagnosis, disease severity and progression, and may help to elucidate pathogenic mechanisms.
authors: Dulbecco Telethon Institute, Milano, Italy.
authors: Giovanni
authors: G
authors: Nardo
authors: Silvia
authors: S
authors: Pozzi
authors: Mauro
authors: M
authors: Pignataro
authors: Eliana
authors: E
authors: Lauranzano
authors: Giorgia
authors: G
authors: Spano
authors: Silvia
authors: S
authors: Garbelli
authors: Stefania
authors: S
authors: Mantovani
authors: Kalliopi
authors: K
authors: Marinou
authors: Laura
authors: L
authors: Papetti
authors: Marta
authors: M
authors: Monteforte
authors: Valter
authors: V
authors: Torri
authors: Luca
authors: L
authors: Paris
authors: Gianfranco
authors: G
authors: Bazzoni
authors: Christian
authors: C
authors: Lunetta
authors: Massimo
authors: M
authors: Corbo
authors: Gabriele
authors: G
authors: Mora
authors: Caterina
authors: C
authors: Bendotti
authors: Valentina
authors: V
authors: Bonetto
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D015203:Reproducibility of Results; D057170:Translational Research, Biomedical
chemical_list: D015415:Biomarkers; D020543:Proteome