Carlo Iannicola

University of Rome Tor Vergata, Roma, Latium, Italy

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Publications (6)37.63 Total impact

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    ABSTRACT: Neuroleukin (NLK) is a multifunctional protein, involved in neuronal growth, glucose metabolism, cell motility, and differentiation. Expressed in the brain, it supports the growth of embryonic spinal, skeletal motor, and sensory neurons. We have previously demonstrated that NLK is up-regulated in the brain during Huntington's disease (HD), a neurodegenerative disorder caused by the expansion of CAG trinucleotide repeats. In order to study the biological role of NLK, we have generated an inducible rat pheochromocytoma PC12 cell line in which the expression of NLK is selectively down-regulated by antisense strategy. We show here that the block of NLK commits PC12 cells to caspase-dependent apoptosis. This priming effect elicited by NLK inhibition is independent from the differentiation state of the neuronal cells. These results suggest a general protective role of NLK in the control of cell death in neuronal cells.
    No preview · Article · Apr 2003 · Biochemical and Biophysical Research Communications
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    ABSTRACT: By crossing Huntington's disease (HD) R6/1 transgenic mice with 'tissue' transglutaminase (TG2) knock-out mice, we have demonstrated that this multifunctional enzyme plays an important role in the neuronal death characterising this disorder in vivo. In fact, a large reduction in cell death is observed in R6/1, TG2(-/-) compared with R6/1 transgenic mice. In addition, we have shown that the formation of neuronal intranuclear inclusions (NII) is potentiated in absence of the 'tissue' transglutaminase. These phenomena are paralleled by a significant improvement both in motor performances and survival of R6/1, TG2(-/-) versus R6/1 mice. Taken together these findings suggest an important role for tissue transglutaminase in the regulation of neuronal cell death occurring in Huntington's disease.
    No preview · Article · Oct 2002 · Cell Death and Differentiation
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    ABSTRACT: Several mouse models for Huntington's disease (HD) have been produced to date. Based on differences in strain, promoter, construct, and number of glutamines, these models have provided a broad spectrum of neurological symptoms, ranging from simple increases in aggressiveness with no signs of neuropathology, to tremors and seizures in absence of degeneration, to neurological symptoms in the presence of gliosis and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling) positivity, and finally to selective striatal damage associated with electrophysiological and behavioral abnormalities. We decided to analyze the morphology of striatum and hippocampus from a mouse transgenic line obtained by microinjection of exon 1 from the HD gene after introduction of a very high number of CAG repeat units. We found a massive darkening and compacting of striatal and hippocampal neurons in affected mice, associated with a lower degree of more classical apoptotic cell condensation. We then explored whether this morphology could be explained with alterations in gene expression by hybridizing normal and affected total brain RNA to a panel of 588 known mouse cDNAs. We show that some genes are significantly and consistently up-regulated and that others are down-regulated in the affected brains. Here we discuss the possible significance of these alterations in neuronal morphology and gene expression.
    No preview · Article · Sep 2000 · Journal of Neurochemistry
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    ABSTRACT: Huntington's disease (HD) is a dominant disorder characterized by premature and progressive neurodegeneration. In order to generate an accurate model of the disease, we introduced an HD-like mutation (an extended stretch of 72–80 CAG repeats) into the endogenous mouse Hdh gene. Analysis of the mutation in vivo reveals significant levels of germline instability, with expansions, contractions and sex-of-origin effects in evidence. Mice expressing full-length mutant protein display abnormal social behaviour in the absence of acute neurodegeneration. Given that psychiatric changes, including irritability and aggression, are common findings in HD patients, our data are consistent with the hypothesis that some clinical features of HD may be caused by pathological processes that precede gross neuronal cell death. This implies that effective treatment of HD may require an understanding and amelioration of these dysfunctional processes, rather than simply preventing the premature death of neurons in the brain. These mice should facilitate the investigation of the molecular mechanisms that underpin the pathway from genotype to phenotype in HD.
    Preview · Article · Jun 1999 · Human Molecular Genetics
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    Full-text · Article · Apr 1999 · Cell Death and Differentiation
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    ABSTRACT: Four point mutations and one insertion within the prion protein (PrP) gene have been tightly linked to the development of inherited prion disease. We developed a denaturing gradient gel electrophoresis system that allowed us to screen the entire open reading frame of the PrP gene. Using this system, we found a new mutation of the PrP gene in a patient with pathologically confirmed Creutzfeldt-Jakob disease and a negative family history for dementia. DNA sequencing revealed an adenine substitution for guanine at the second position of codon 208, which results in the nonconservative substitution of histidine for arginine. The same PrP mutation was identified in another younger member of the pedigree but was not present in more than 200 alleles tested. Such findings suggest that the frequency of inherited prion disease might be higher than ascertained by clinical history alone.
    No preview · Article · Dec 1996 · Neurology