Data di Pubblicazione:
2017
Citazione:
Dissecting Sporadic ALS in a geographical cluster of patients: a multidisciplinary study / S. De Benedetti, G. Lucchini, A. Marocchi, S. Penco, C. Lunetta, S. Iametti, E. Gianazza, F. Bonomi. ((Intervento presentato al convegno Young Scientific Forum and 47th FEBS congress tenutosi a Gerusalemme nel 2017.
Abstract:
Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disorder that results
in paralysis and leading to death in 3-5 years. Genetic and environmental factors are
involved in the pathogenesis of this disease and metals metabolism has been linked to
ALS. Proteomic studies are currently being performed to search for possible
biomarkers. Here we present a study aimed at investigating different aspects of the
disease, based on a multidisciplinary approach. The cohort of ALS patients that we
analyzed includes seven patients, all originating from a common, restricted,
geographical area and five matched controls. Environmental exposure is the same for
all these subjects.
SOD1, FUS, TDP43, C9ORF72 and APOE genotypes were evaluated. For metal quantitation,
samples of serum and whole blood were analyzed by ICP-MS. For proteomic analyses,
immobilized pH gradient covered the 4-10 and 3-7 pH range both in reducing and nonreducing
conditions. Levels of DNA oxidation were evaluated by a comet assay.
Statistical analyses were carried out with Student’s t-test and Artificial Neural
Networks.
As concentration resulted significantly lower in patients than in controls ( Auto-CM
analysis linked closely high concentrations of Al and Se to the ALS group. Levels of
metals in whole blood have been correlated with levels in serum.
Proteomics data show that some proteins related to Acute Phase Response (APR) and
lipid homeostasis are decreased in patients. Apoε4 allele is more represented in the
patient’s group than in controls’.
Impaired metal homeostasis, attributable to environmental exposure, could lead to
mineral overload. Metals can compete for the binding sites of metal-containing
proteins. The different expression of the APR proteins reported could be a reflection
of the disease status of the subjects analyzed. Enrichment in Apoε4 allele frequency
in patients may provide a link between neurodegeneration and lipid metabolism
disturbances.
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Elenco autori:
S. De Benedetti, G. Lucchini, A. Marocchi, S. Penco, C. Lunetta, S. Iametti, E. Gianazza, F. Bonomi
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