1,989 research outputs found
CELL GROWTH AND CHOLESTEROL ESTERS
No full textIn recent years, understanding the molecular mechanisms involved in
intracellular cholesterol homeostasis has radically changed to include an
increasing number of structurally diverse receptors and carriers. The latest
additions have led to the implication of cholesterol in fundamental cell functions
such as cellular signaling and growth regulation. It appears that, at
least in some instances, adaptive regulation of cholesterol metabolism does
not protect cells indefinitely. Changes in this fine homeostatic regulation
may occur leading to pathologic consequences. The challenge of this book
has been to provide a useful point of reference on the mechanisms that
link cholesterol esters to cell growth and division. Particular attention has
been dedicated to the alterations in cholesterol esterification in two important
proliferative processes such as cancer and atherosclerosis.
The data presented in this book provide in vivo and in vitro evidence
of a strong relationship between cholesterol esterification and rate of cell
proliferation, and suggest that changes in the cholesterol esterification pathway
might represent fundamental events in developmental growth processes.
Although much progress has been made in tumor and atherosclerosis research,
and remarkable therapeutic successes have been achieved in both
these pathologies, several questions on the mechanisms underlying changes
in cholesterol metabolism and cell proliferation remain to be answered. Therefore,
the data acquire particular significance in view of the possibility that
the overall process of cholesterol esterification could play a key role in regulating
cell proliferation.
We hope that this book provides valuable information not only for
physicians, but also for teachers and students. As for the Editors, we would
like to look at this book as a milestone of a path started some seven years ago
when two friends, even though not so young any more, still deeply fascinated
by science and the potentiality of biology, put together their scientific
competence to face important matters such as the pharmacological control
of pathological proliferative processes from a novel perspective.
Alessandra Pani
Sandra Dessi
Anti-HIV-1 integrase drugs:how far from the shelf?
No full textChemotherapy of HIV-I infection/AIDS currently employs inhibitors of two products of the viral pol gene, the reverse transcriptase acid protease enzymes. However, a third product of the pol gene is essential for retroviral multiplication, the integrase. As no cellular homologue of HIV integrase has been described, potential inhibitors could be relatively nontoxic. Development of HIV-1 integrase inhibitors could have favorable implication for combination therapy, including potential synergy with currently available inhibitors, as well as prevention of the chronic carrier state and the emergence of resistant mutants. Although several classes of putative integrase inhibitors that been described, still no clinically useful anti-integration drugs are available. It is the structural and functional complexity of the integration process together with the limitations of the available in vitro assays that has made it problematic to develop inhibitors of the HIV integrase. In this review we summarize current knowledge concerning the biology of this enzyme and of the integration process, and discuss major classes representatives of integrase inhibitors considering the obstacles to the development of true anti-integrase drugs
Cholesterol, Alzheimer’s Disease, Prion Disorders: a ménage à trois?
No full textAberrant folded proteins are hallmarks of amyloidogenic diseases. Examples are Alzheimer's disease (AD) and
prion-related disorders (PrD). These disorders, although clinically different, have the same underlying pathogenetic
mechanism: an altered protein conformer with high β-sheet structure content: the amyloid beta peptide (Aβ) in the case of AD, and the aberrant prion protein, PrPsc in PrD. Although the molecular processes that cause these proteins to adopt
non-native structures in vivo and become cytotoxic are still largely unknown, there is good reason to expect prion research to profit from advances in the understanding of AD, and vice versa. Growing evidence indicates that the various pathways
of lipid/lipoprotein metabolism play a key role in AD and PrD pathophysiology. These findings clearly highlight the possible involvement of cholesterol in misfolded protein generation. In this review, we focus on recent studies which provide evidence that membrane domains, called lipid rafts, directly promote protein misfolding, and that this process takes place only if changes occur in the fine regulation of intracellular cholesterol. In addition, we discuss the implications
of these results to introduce the concept that pharmacological interventions restoring cholesterol homeostasis could have
potential preventive/therapeutic value against the progression of misfolding disorders. The aim of the review is to provide
researchers with a general understanding of cholesterol’s involvement in protein folding/misfolding processes which may be relevant for knowledge advancement regarding amyloidogenic proteins, and possible ways to prevent their pathological activity
Therapeutical compositions having anti-HIV activity consisting of 2', 3'-didesoxyadenosine and substances inhibiting adenosine deaminase.
No full textTherapeutical compositions, having enhanced anti-HIV activity consisting of 2', 3'-didesoxy-
adenosine and of substances inhibiting the adenosine-deaminase selected from the group
consisting of 9-(erythro-2-hydroxy-3-nonyl) adenine (EHNA), 3-deaza-EHNA, coformycin,
desoxycoformycin, 1-deaza-EHNA, 1, 3-dideaza-EHNA and 7-deaza-EHNA
Cholesterol homeostasis: a key to prevent or slow down neurodegeneration
No full textNeurodegeneration, a common feature for many brain disorders, has severe consequences on the mental and physical health of an individual. Typically human neurodegenerative diseases are devastating illnesses that predominantly affect elderly people, progress slowly, and lead to disability and premature death; however they may occur at all ages. Despite extensive research and investments, current therapeutic interventions against these disorders treat solely the symptoms. Therefore, since the underlying mechanisms of damage to neurons are similar, in spite of etiology and background heterogeneous, it will be of interest to identify possible trigger point of neurodegeneration enabling development of drugs and/or prevention strategies that target many disorders simultaneously. Among the factors that have been identified so far to cause neurodegeneration, failures in cholesterol homeostasis are indubitably the best investigated. The aim of this review is to critically discuss some of the main results reported in the recent years in this field mainly focusing on the mechanisms that, by recovering perturbations of cholesterol homeostasis in neuronal cells, may correct clinically relevant features occurring in different neurodegenerative disorders and, in this regard, also debate the current potential therapeutic interventions
Lettera di Alessandra
No full textUn ritratto critico dell'opera di Alessandra Carnaroli, autrice fra le più apprezzate delle ultime generazioni della poesia di ricerca. La sezione a lei dedicata, nel numero della rivista, contiene inoltre saggi di Cecilia Bello Minciacchi, Andrea Cortellessa, e Ivan Schiavone; e vari inediti dell'autrice. Il saggio è pubblicato con lo pseudonimo di Tommaso Ottonieri.A critical portrait of the work of Alessandra Carnaroli, author of the most appreciated in the latest generations of italian research poetry. Published under the pseudonym Tommaso Ottonieri
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