Antonio Indaco - Academia.edu (original) (raw)
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Shahid Beheshti University of Medical Sciences
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Papers by Antonio Indaco
PLoS pathogens, 2015
Prions are infectious proteins that possess multiple self-propagating structures. The information... more Prions are infectious proteins that possess multiple self-propagating structures. The information for strains and structural specific barriers appears to be contained exclusively in the folding of the pathological isoform, PrPSc. Many recent studies determined that de novo prion strains could be generated in vitro from the structural conversion of recombinant (rec) prion protein (PrP) into amyloidal structures. Our aim was to elucidate the conformational diversity of pathological recPrP amyloids and their biological activities, as well as to gain novel insights in characterizing molecular events involved in mammalian prion conversion and propagation. To this end we generated infectious materials that possess different conformational structures. Our methodology for the prion conversion of recPrP required only purified rec full-length mouse (Mo) PrP and common chemicals. Neither infected brain extracts nor amplified PrPSc were used. Following two different in vitro protocols recMoPrP ...
Brain Pathology, 2012
In Creutzfeldt-Jakob disease (CJD), molecular typing based on the size of the protease resistant ... more In Creutzfeldt-Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrP Sc ) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrP Sc and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrP Sc are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia.
Prion diseases include sporadic, acquired and genetic forms linked to mutations of the prion prot... more Prion diseases include sporadic, acquired and genetic forms linked to mutations of the prion protein (PrP) gene (PRNP). In subjects carrying the D178N PRNP mutation, distinct phenotypes can be observed, depending on the methionine/valine codon 129 polymorphism. We present here a 53-year-old woman with D178N mutation in the PRNP gene and homozygosity for valine at codon 129. The disease started at age 47 with memory deficits, progressive cognitive impairment and ataxia. The clinical picture slowly worsened to a state of akinetic mutism in about 2 years and the disease course was 6 years. The neuropathologic examination demonstrated severe diffuse cerebral atrophy with neuronal loss, spongiosis and marked myelin loss and tissue rarefaction in the hemispheric white matter, configuring panencephalopathic Creutzfeldt-Jakob disease. PrP deposition was present in the cerebral cortex, basal ganglia and cerebellum with diffuse synaptic-type pattern of immunoreactivity and clusters of countless, small PrP deposits, particularly evident in the lower cortical layers, in the striatum and in the molecular layer of the cerebellum. Western blot analysis showed the presence of type 1 PrP(Sc) (Parchi classification). These findings underline the clear-cut distinction between the neuropathological features of Creutzfeldt-Jakob disease associated with D178N PRNP mutation and those of fatal familial insomnia.
Acta Neuropathologica, 2012
Ab is the main component of amyloid deposits in Alzheimer disease (AD) and its aggregation into o... more Ab is the main component of amyloid deposits in Alzheimer disease (AD) and its aggregation into oligomers, protofibrils and fibrils is considered a seminal event in the pathogenesis of AD. Ab with C-terminus at residue 42 is the most abundant species in parenchymal deposits, whereas Ab with C-terminus at residue 40 predominates in the amyloid of the walls of large vessels. Ab peptides with other C-termini have not yet been thoroughly investigated. We analysed Ab38 in the brains of patients with Ab deposition linked to sporadic and familial AD, hereditary cerebral haemorrhage with amyloidosis, or Down syndrome. Immunohistochemistry, confocal microscopy, immunoelectron microscopy, immunoprecipitation and the electrophoresis separation of low molecular weight aggregates revealed that Ab38 accumulates consistently in the brains of patients carrying APP mutations in the Ab coding region, but was not detected in the patients with APP mutations outside the Ab domain, in the patients with presenilin mutations or in subjects with Down syndrome. In the patients with sporadic AD, Ab38 was absent in the senile plaques, but it was detected only in the vessel walls of a small subset of patients with severe cerebral amyloid angiopathy. Our results suggest that APP mutations in the Ab coding region favour Ab38 accumulation in the brain and that the molecular mechanisms of Ab deposition in these patients may be different from those active in patients with familial AD associated with other genetic defects and sporadic AD.
PLoS pathogens, 2015
Prions are infectious proteins that possess multiple self-propagating structures. The information... more Prions are infectious proteins that possess multiple self-propagating structures. The information for strains and structural specific barriers appears to be contained exclusively in the folding of the pathological isoform, PrPSc. Many recent studies determined that de novo prion strains could be generated in vitro from the structural conversion of recombinant (rec) prion protein (PrP) into amyloidal structures. Our aim was to elucidate the conformational diversity of pathological recPrP amyloids and their biological activities, as well as to gain novel insights in characterizing molecular events involved in mammalian prion conversion and propagation. To this end we generated infectious materials that possess different conformational structures. Our methodology for the prion conversion of recPrP required only purified rec full-length mouse (Mo) PrP and common chemicals. Neither infected brain extracts nor amplified PrPSc were used. Following two different in vitro protocols recMoPrP ...
Brain Pathology, 2012
In Creutzfeldt-Jakob disease (CJD), molecular typing based on the size of the protease resistant ... more In Creutzfeldt-Jakob disease (CJD), molecular typing based on the size of the protease resistant core of the disease-associated prion protein (PrP Sc ) and the M/V polymorphism at codon 129 of the PRNP gene correlates with the clinico-pathologic subtypes. Approximately 95% of the sporadic 129MM CJD patients are characterized by cerebral deposition of type 1 PrP Sc and correspond to the classic clinical CJD phenotype. The rare 129MM CJD patients with type 2 PrP Sc are further subdivided in a cortical and a thalamic form also indicated as sporadic fatal insomnia.
Prion diseases include sporadic, acquired and genetic forms linked to mutations of the prion prot... more Prion diseases include sporadic, acquired and genetic forms linked to mutations of the prion protein (PrP) gene (PRNP). In subjects carrying the D178N PRNP mutation, distinct phenotypes can be observed, depending on the methionine/valine codon 129 polymorphism. We present here a 53-year-old woman with D178N mutation in the PRNP gene and homozygosity for valine at codon 129. The disease started at age 47 with memory deficits, progressive cognitive impairment and ataxia. The clinical picture slowly worsened to a state of akinetic mutism in about 2 years and the disease course was 6 years. The neuropathologic examination demonstrated severe diffuse cerebral atrophy with neuronal loss, spongiosis and marked myelin loss and tissue rarefaction in the hemispheric white matter, configuring panencephalopathic Creutzfeldt-Jakob disease. PrP deposition was present in the cerebral cortex, basal ganglia and cerebellum with diffuse synaptic-type pattern of immunoreactivity and clusters of countless, small PrP deposits, particularly evident in the lower cortical layers, in the striatum and in the molecular layer of the cerebellum. Western blot analysis showed the presence of type 1 PrP(Sc) (Parchi classification). These findings underline the clear-cut distinction between the neuropathological features of Creutzfeldt-Jakob disease associated with D178N PRNP mutation and those of fatal familial insomnia.
Acta Neuropathologica, 2012
Ab is the main component of amyloid deposits in Alzheimer disease (AD) and its aggregation into o... more Ab is the main component of amyloid deposits in Alzheimer disease (AD) and its aggregation into oligomers, protofibrils and fibrils is considered a seminal event in the pathogenesis of AD. Ab with C-terminus at residue 42 is the most abundant species in parenchymal deposits, whereas Ab with C-terminus at residue 40 predominates in the amyloid of the walls of large vessels. Ab peptides with other C-termini have not yet been thoroughly investigated. We analysed Ab38 in the brains of patients with Ab deposition linked to sporadic and familial AD, hereditary cerebral haemorrhage with amyloidosis, or Down syndrome. Immunohistochemistry, confocal microscopy, immunoelectron microscopy, immunoprecipitation and the electrophoresis separation of low molecular weight aggregates revealed that Ab38 accumulates consistently in the brains of patients carrying APP mutations in the Ab coding region, but was not detected in the patients with APP mutations outside the Ab domain, in the patients with presenilin mutations or in subjects with Down syndrome. In the patients with sporadic AD, Ab38 was absent in the senile plaques, but it was detected only in the vessel walls of a small subset of patients with severe cerebral amyloid angiopathy. Our results suggest that APP mutations in the Ab coding region favour Ab38 accumulation in the brain and that the molecular mechanisms of Ab deposition in these patients may be different from those active in patients with familial AD associated with other genetic defects and sporadic AD.