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Burti L.,University of VeronaVerona
International Journal of Mental Health

Abstract: There is no mental health without respect for the dignity of mental patients on an equal basis with all other citizens. Rehabilitation is no exception, and deinstitutionalization is its necessary prerequisite. Italy has embraced these principles its 1978 mental health reform, which did away with the mental hospital. After thirty-plus years of community psychiatry, the nation has now the opportunity of exploring further enlightening developments of rehabilitation in the never-ending process of promoting the role of mental patients in society at large. © 2016, Copyright © Taylor & Francis Group, LLC. Source

Montioli R.,University of VeronaVerona | Oppici E.,University of VeronaVerona | Dindo M.,University of VeronaVerona | Roncador A.,University of VeronaVerona | And 4 more authors.
Biochimica et Biophysica Acta - Proteins and Proteomics

Abstract Liver peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5′-phosphate (PLP) enzyme, exists as two polymorphic forms, the major (AGT-Ma) and the minor (AGT-Mi) haplotype. Deficit of AGT causes Primary Hyperoxaluria Type 1 (PH1), an autosomal recessive rare disease. Although ∼ one-third of the 79 disease-causing missense mutations segregates on AGT-Mi, only few of them are well characterized. Here for the first time the molecular and cellular defects of G47R-Mi are reported. When expressed in Escherichia coli, the recombinant purified G47R-Mi variant exhibits only a 2.5-fold reduction of its kcat, and its apo form displays a remarkably decreased PLP binding affinity, increased dimer-monomer equilibrium dissociation constant value, susceptibility to thermal denaturation and to N-terminal region proteolytic cleavage, and aggregation propensity. When stably expressed in a mammalian cell line, we found ∼ 95% of the intact form of the variant in the insoluble fraction, and proteolyzed (within the N-terminal region) and aggregated forms both in the soluble and insoluble fractions. Moreover, the intact and nicked forms have a peroxisomal and a mitochondrial localization, respectively. Unlike what already seen for G41R-Mi, exposure of G47R-Mi expressing cells to pyridoxine (PN) remarkably increases the expression level and the specific activity in a dose-dependent manner, reroutes all the protein to peroxisomes, and rescues its functionality. Although the mechanism of the different effect of PN on the variants G47R-Mi and G41R-Mi remains elusive, the chaperoning activity of PN may be of value in the therapy of patients bearing the G47R mutation. © 2015 The Authors. Source

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