Luca Colucci D'Amato

Luca Colucci D'Amato
Università degli Studi della Campania "Luigi Vanvitelli

Professor

About

89
Publications
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Publications

Publications (89)
Article
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Glioblastoma (GBM) is the most aggressive type of brain tumor, characterized by poor outcome and limited therapeutic options. During tumor progression, GBM may undergo the process of vasculogenic mimicry (VM), consisting of the formation of vascular-like structures which further promote tumor aggressiveness and malignancy. The resulting resistance...
Article
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Simple Summary Glioblastoma is the most devastating and widespread primary central nervous system tumor and there is a compelling need for innovative and effective therapeutic strategies. The remarkable vascularization sustaining this malignancy occurs through different mechanisms, including vasculogenic mimicry, i.e., the non-endothelial formation...
Article
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Introduction and aims The limited therapeutic options for ischemic stroke treatment render necessary the identification of new strategies. In recent years, it has been shown that natural compounds may represent a valid therapeutic opportunity. Therefore, the present study aimed to evaluate the protective effect of Ruta graveolens water extract (RGW...
Article
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Multiple sclerosis is a chronic disease of the central nervous system characterized by demyelination and destruction of axons. The most common form of the disease is the relapsing-remitting multiple sclerosis in which episodic attacks with typical neurological symptoms are followed by episodes of partial or complete recovery. One of the underestima...
Article
ZBTB2 is a protein belonging to the BTB/POZ zinc-finger family whose members typically contain a BTB/POZ domain at the N-terminus and several zinc-finger domains at the C-terminus. Studies have been carried out to disclose the role of ZBTB2 in cell proliferation, in human cancers and in regulating DNA methylation. Moreover, ZBTB2 has been also desc...
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Neural stem cells represent a powerful tool to study molecules involved in pathophysiology of Nervous System and to discover new drugs. Although they can be cultured and expanded in vitro as a primary culture, their use is hampered by their heterogeneity and by the cost and time needed for their preparation. Here we report that mes-c-myc A1 cells (...
Article
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Brain-derived neurotrophic factor (BDNF) is one of the most distributed and extensively studied neurotrophins in the mammalian brain. BDNF signals through the tropomycin receptor kinase B (TrkB) and the low affinity p75 neurotrophin receptor (p75NTR). BDNF plays an important role in proper growth, development, and plasticity of glutamatergic and GA...
Article
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The relatively few dopaminergic neurons in the mammalian brain are mostly located in the midbrain and regulate many important neural functions, including motor integration, cognition, emotive behaviors and reward. Therefore, alteration of their function or degeneration leads to severe neurological and neuropsychiatric diseases. Unraveling the mecha...
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Nutraceuticals had always been known for their therapeutic effects in ancient medicine and had been the primary healing remedy until the introduction of modern chemistry and pharmacology. However, their use has not been dismissed but actually is acquiring a new acclamation among the scientific community especially for their efficacy on the Central...
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Premise Headaches are a serious public health concern of our days, affecting about 50% of the world’s adult population. However, such a plague is not limited to the modern era, since ancient archaeological, written, religious and cultural evidences testify to countless attempts to face such disorders from medical, neurosurgical, psychological and s...
Conference Paper
Neural stem cells (NSCs) proliferation and differentiation play a pivotal role in the generation of functional neuronal networks. However, NSCs as they develop and acquire the features of a mature neuronal phenotype progressively lose their ability to proliferate. Here we demonstrate that Ruta graveolens aqueous extract (R. graveolens a.e.), which...
Article
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Angiogenesis is a phenomenon that includes different processes, such as endothelial cell proliferation, differentiation, and migration, that lead to the formation of new blood vessels and involve several signal transduction pathways. Here we show that the tube formation assay is a simple in vitro method to evaluate the impact of natural products on...
Article
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Glioblastoma (GBM), a high-grade glioma (WHO grade IV), is the most aggressive form of brain cancer. Available treatment options for GBM involve a combination of surgery, radiation and chemotherapy but result in a poor survival outcome. GBM is a high-vascularized tumor and antiangiogenic drugs are widely used in GBM therapy as adjuvants to control...
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Differential DNA methylation defects of H19/IGF2 are associated with congenital growth disorders characterized by opposite clinical pictures. Due to structural differences between human and mouse, the mechanisms by which mutations of the H19/IGF2 Imprinting Control region (IC1) result in these diseases are undefined. To address this issue, we previ...
Data
(Related to Fig 2). Phenotypic characterization of H19hIC1/+ mice. Box plots of birth weights (A), growth charts (B), and box plots of organ weights (C) of H19hIC1/+ mice and H19+/+ littermates. Box plots in (A) and (C) and growth chart in (B) are depicted as in Fig 2. Values in brackets indicate the number of animals derived from two (A and C) or...
Data
Primers and PCR conditions of the pyosequencing assay. hIC1-:primers to amplify the human IC1 of the knock-in. mIC-: primers to amplify the mouse IC1 and IC2. F (Forward), R (Reverese): PCR primers. Seq: primers for sequencing; Btn: 5’ biotinylated primer. (DOCX)
Data
Stability of IC1 methylation of H19hIC1Δ2.2/+ mice after consecutive passages through the female germline. Percent methylation measured by pyrosequencing at two CTCF target sites (CTS1 and CTS6) in three different organs collected from H19hIC1Δ2.2/+ mice derived from three successive generations of breeding H19hIC1Δ2.2/+ females with +/+ males (II,...
Data
Analysis of H19 and Igf2 expression in H19+/hIC1Δ2.2 and H19+/hIC1 mice at E15.5. (A-B) Histograms of total H19 and Igf2 expression in embryo body and placenta of H19+/hIC1Δ2.2 (A) and H19+/hIC1 (B) mice at E15.5 compared to relative H19+/+ littermates, analysed as in Fig 3. (C-D) Allele-specific expression of H19 and Igf2 in in embryo body and pla...
Data
Absence of kidneys asymmetry in H19hIC1/+ mice. Weight ratio of the heavier to the lighter kidney in H19hIC1/+ and their +/+ littermates derived from two litters at 12 weeks-old mice. (TIF)
Data
(Related to Fig 3). Analysis of H19 and Igf2 expression in H19hIC1/+ newborn mice. (A) Allele-specific expression of H19 and Igf2 analysed as in Fig 3. (B) Histograms of total H19 and Igf2 expression in three different neonatal organs of H19hIC1/+ and H19+/+ littermates. The animals used for this study derived from two litters. (TIF)
Data
IC1 methylation in H19+/hIC1Δ2.2 mice. (A) See legend to Fig 4A. (B) Percent methylation measured by pyrosequencing at CTS1 and CTS6 in three different organs collected from H19+/hIC1Δ2.2 mice at birth (left panel). The endogenous mIC1 was analysed as in Fig 3. Each histogram represents the methylation mean value of 5 (CTS1 and mIC1) or 6 (CTS6) Cp...
Data
Stability of hIC1Δ2.2 methylation through the male germline and after the passage from female to male germline. (A) Percent methylation measured by pyrosequencing at two CTCF target sites (CTS1 and CTS6) in three different organs collected from H19+/hIC1Δ2.2 mice of three successive generations of breeding H19+/hIC1Δ2.2 males with +/+ females (II,...
Article
Angiogenesis is a process encompassing several steps such as endothelial cells proliferation, differentiation and migration to form a vascular network, involving different signal transduction pathways. Among these, ERK1/2 signaling mediates VEGF-dependent signaling pathway. Here we report that the water extract of Ruta graveolens (RGWE), widely kno...
Article
Full-text available
Tryptophan hydroxylase 2 ( TPH 2) is the key enzyme in the synthesis of neuronal serotonin . Although previous studies suggest that TPH 2 neuron‐restrictive silencer element ( NRSE ) functions as a negative regulator dependent on neuron‐restrictive silencer factor ( NRSF ) activity, the underlying mechanisms are yet to be fully elucidated. Here, we...
Article
Progranulin (GRN) gene mutations have been genetically associated with FTD and are present in about 23% of patients with familial FTD. However, the neurobiology of this secreted glycoprotein remains unclear. Here, we report the identification of three pedigrees of Southern Italian extraction in whom FTD segregates with autosomal dominant inheritanc...
Article
We performed ultra-deep methylation analysis at single molecule level of the promoter region of developmentally regulated D-Aspartate oxidase (Ddo), as a model gene, during brain development and embryonic stem cell neural differentiation. Single molecule methylation analysis enabled us to establish the effective epiallele composition within mixed o...
Article
Activation of microglia is a central event in the atypical inflammatory response occurring during prion encephalopathies. We report that the prion protein fragment encompassing amino acids 90-231 (PrP90-231), a model of the neurotoxic activity of the pathogenic prion protein (PrP(Sc)), causes activation of both primary microglia cultures and N9 mic...
Article
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Glioblastoma multiforme is a highly aggressive brain tumor whose prognosis is very poor. Due to early invasion of brain parenchyma, its complete surgical removal is nearly impossible, and even after aggressive combined treatment (association of surgery and chemo- and radio-therapy) five-year survival is only about 10%. Natural products are sources...
Article
Chemokines and cytokines, primarily known for their roles in the immune and inflammatory response, have also been identified as key components of the neurogenic niche where they are involved in the modulation of neural stem cells proliferation and differentiation. However, a complete understanding of the functional role played in neural differentia...
Article
Neural stem cell proliferation and differentiation play a crucial role in the formation and wiring of neuronal connections forming neuronal circuits. During neural tissues development, a large diversity of neuronal phenotypes is produced from neural precursor cells. In recent years, the cellular and molecular mechanisms by which specific types of n...
Article
Serotonin (5-HT) is a neurotransmitter involved in many aspects of the neuronal function. The synthesis of 5-HT is initiated by the hydroxylation of tryptophan, catalyzed by tryptophan hydroxylase (TPH). Two isoforms of TPH (TPH1 and TPH2) have been identified, with TPH2 almost exclusively expressed in the brain. Following TPH2 discovery, it was re...
Article
Huntingtin (htt) is a scaffold protein localized at the subcellular level and is involved in coordinating the activity of several protein for signaling and intracellular transport. The emerging properties of htt in intracellular trafficking prompted us to study the role of mutant htt (polyQ-htt) in the intracellular fate of epidermal growth factor...
Article
Phospholipases (PLA2s) are a superfamily of enzymes characterized by the ability to specifically hydrolyze the sn-2 ester bond of phospholipids generating arachidonic acid, utilized in inflammatory responses, and lysophospholipids involved in the control of cell membrane remodeling and fluidity. PLA2s have been so far considered a crucial element i...
Article
Tau is a multifunctional protein detected in different cellular compartments in neuronal and non-neuronal cells. When hyperphosphorylated and aggregated in atrophic neurons, tau is considered the culprit for neuronal death in familial and sporadic tauopathies. With regards to Alzheimer's disease (AD) pathogenesis, it is not yet established whether...
Article
Krüppel-like factor 7 (KLF7) belongs to the large family of KLF transcription factors, which comprises at least 17 members. Within this family, KLF7 is unique since its expression is strictly restricted within the nervous system during development. We have previously shown that KLF7 is required for neuronal morphogenesis and axon guidance in select...
Article
Una delle iniziali interpretazioni della plasticità nel SN veniva dalle osservazioni che la trasmissione sinaptica non è rigida ma può essere regolata. Questa plasticità è alla base dei cambiamenti adattativi dei diversi circuiti. Tutti i meccanismi di plasticità sinaptica nell’adulto si basano su meccanismi di rafforzamento o indebolimento delle s...
Article
Le cellule staminali rappresentano oggi uno dei campi più importanti della ricerca bio-medica per lo studio dei meccanismi di sviluppo embrionale e di quelli patogenetici e per la messa a punto di nuove terapie cellulari nel quadro di quella che oggi si chiama “medicina rigenerativa”.
Article
Il premio Nobel per la Medicina e Fisiologia del 1960, l’immunologo Sir Peter Medawar, per spiegare la complessità del sistema endocrino e come si fosse giunti ad essa attraverso l’evoluzione, scriveva “endocrine evolution is not an evolution of hormones but an evolution of the uses to which they are put; an evolution not, to put it crudely, of che...
Article
Nel cranio e nel canale vertebrale, sedi del SNC, sono contenute cellule che derivano dal neuroectoderma (cellule neurali) e, inoltre, alcuni tipi cellulari che, pur non appartenendo embriologicamente al SN, sono in stretta relazione anatomica e funzionale con esso e verrano di seguito descritti.
Article
La chiave delle neuroscienze moderne risiede nel principio che sia le funzioni nervose semplici, come quella di un verme che si muove verso una fonte di cibo, sia quelle complesse, quali l’elaborazione articolata del pensiero e dell’ideazione nei primati superiori (l’uomo), siano la conseguenza dell’attività di specifici componenti molecolari all’i...
Article
Gli agenti eziologici che sono in grado di ledere il SNC non sono di per sé diversi da quelli che determinano le malattie in altri organi o apparati del corpo umano. Il Sistema Nervoso, infatti, al pari di altri distretti dell’organismo, può ammalarsi a causa di traumi, può andare incontro a infiammazione, infezioni, può manifestare disturbi vascol...
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I neurobiologi, e la gran parte dei neurologi, psichiatri e psicoanalisti, concordano nel ritenere che la “coscienza”, come anche il pensiero, la memoria, l’apprendimento, le emozioni, l’immaginazione, la paura, l’ansia, sono determinati dall’attività elettrica di grandi gruppi di neuroni. Gli studi degli ultimi decenni hanno dimostrato che i quasi...
Article
I fattori neurotrofici (FN) (dal greco trofein concernente il nutrimento) sono molecole solubili di natura proteica che, secrete da cellule di vario tipo (neuroni, glia, cellule emopoietiche, ecc.), favoriscono la sopravvivenza dei neuroni (cellule bersaglio, target cells). Essi agiscono su specifici recettori di membrana posti sulle cellule bersag...
Article
L’insieme dei gangli della base (GB) costituisce un sistema (o sistemi) così complesso che è stato definito, parafrasando Winston Churchill, “un indovinello avvolto nel mistero, dentro un enigma”.
Chapter
Il SN è didatticamente suddiviso in centrale e periferico pur essendoci continuità anatomica fra i due. Il SNC è formata dall’insieme delle strutture centralizzate nella scatola cranica e nel canale vertebrale, encefalo e midollo spinale rispettivamente, poste in continuià fra loro. Encefalo e midollo spinale sono anche indicati come nevrasse del q...
Article
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Previous gene targeting studies in mice have implicated the nuclear protein Krüppel-like factor 7 (KLF7) in nervous system development while cell culture assays have documented its involvement in cell cycle regulation. By employing short hairpin RNA (shRNA)-mediated gene silencing, here we demonstrate that murine Klf7 gene expression is required fo...
Article
Mechanisms underlying neural stem cell proliferation, differentiation and maturation play a critical role in the formation and wiring of neuronal connections. This process involves the activation of multiple serial events, which guide the undifferentiated cells to different lineages via distinctive developmental programs, forming neuronal circuits...
Article
The proteomic profiling, by means of label-free qualitative and quantitative LC-MS analysis of proliferating/undifferentiated vs nonproliferating/differentiated mes-c-myc A1 cell line (A1), has been performed. A1 cells were generated from mouse embryonic central nervous system. The study was aimed at surveying the molecular changes following neural...
Article
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The discovery of neurogenesis and neural stem cells (NSC) in the adult CNS has overturned a long-standing and deep-routed "dogma" in neuroscience, established at the beginning of the 20(th) century. This dogma lasted for almost 90 years and died hard when NSC were finally isolated from the adult mouse brain. The scepticism in accepting adult neurog...
Article
The glial cell line-derived neurotrophic factor (GDNF) exerts trophic actions on a number of cell types, including mesencephalic dopaminergic (mDA) neurons. Using rat mesencephalic primary cultures enriched in mDA neurons, we show that protracted GDNF stimulation increases their survival and neurite outgrowth. It modulates the expression of genes e...
Article
The transcription factor Nurr1 is essential for the generation of midbrain dopaminergic neurons (mDA). Only a few Nurr1-regulated genes have so far been identified and it remains unclear how Nurr1 influences the development and function of dopaminergic neurons. To identify novel Nurr1 target genes we have used genome-wide expression profiling in ra...
Article
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Serotonin (5-HT) is a neurotransmitter involved in a variety of CNS functions during development and in adulthood. 5-HT neurons are also involved in the pathogenesis of a number of psychiatric disorders. FLUOXETINE (FLX), a prototypic antidepressant, is a selective 5-HT uptake inhibitor (SSRI) with a demonstrated clinical efficacy in these disorder...
Article
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Until the 1990s, neurologists were practising their profession under the doctrine established in the late 19th to early 20th century by the prominent histologist Ramon y Cajal: "Once the development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably. In the adult centers, the nerve paths are something f...
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The growth cycle in nutrient-rich, aquatic environments starts with a diatom bloom that ends in mass sinking of ungrazed cells and phytodetritus. The low grazing pressure on these blooms has been attributed to the inability of overwintering copepod populations to track them temporally. We tested an alternative explanation: that dominant diatom spec...
Article
The transcription factor/nuclear receptor Nurr1 is essential for the differentiation of midbrain dopaminergic neurones. Here we demonstrate that, during the ontogeny of rat ventral mesencephalon, nurr1 gene expression is developmentally regulated and its levels show a sharp peak between embryonic day E13 and E15, when most dopaminergic neurones dif...
Article
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We analyzed the molecular mechanisms involved in the acquisition and maturation of dopaminergic (DA) neurons generated in vitro from rat ventral mesencephalon (MES) cells in the presence of mitogens or specific signaling molecules. The addition of basic fibroblast growth factor (bFGF) to MES cells in serum-free medium stimulates the proliferation o...
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Ecophysiology Laboratory, Stazione Zoologica A. Dohrn, Villa Comunale, 80121 Naples, Italy. ianora@szn.it The growth cycle in nutrient-rich, aquatic environments starts with a diatom bloom that ends in mass sinking of ungrazed cells and phytodetritus. The low grazing pressure on these blooms has been attributed to the inability of overwintering cop...
Article
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The extracellular-signal regulated kinases 1/2 (ERK or ERKs) are involved in the regulation of important neuronal functions, including neuronal plasticity in normal and pathological conditions. We present findings that support the notion that the kinetics and localization of ERK are intrinsically linked, in that the duration of ERK activation dicta...
Article
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Kainate (KA) receptors are a family of ionotropic glutamate receptors, which mediate the excitatory synaptic transmission in various areas of the mammalian CNS. We have studied the expression pattern of the genes encoding for KA receptor subunits (Glur5-1, Glur5-2, Glur6, Glur7, KA1 and KA2) in rat prenatal (E), postnatal and adult ventral mesencep...
Article
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There are always more evidences indicating that 17beta-estradiol (E(2)) is necessary for normal male fertility. We have used a nonmammalian vertebrate model (the lizard Podarcis s. sicula) to investigate the regulation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) activity in the testis during the annual sexual cycle and to study whethe...
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Several lines of evidences support a key role of extracellular regulated-signal kinase 1 and 2 (ERK1/2) in male fertility. Using a non-mammalian vertebrate model, the frogRana esculenta, we have investigated the regulation of ERK1/2 activity in the testis during the annual sexual cycle. ERK1/2 proteins (molecular weight 44 and 42 kDa respectively)...
Article
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Several lines of evidence support a key role of estradiol-17beta (E(2)) in male fertility. We have used a non-mammalian vertebrate model, the frog Rana esculenta, to investigate the regulation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) activity in the testis during the annual sexual cycle and to study whether E(2 )exerts a role in sp...
Article
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Oncogenic variants of the receptor tyrosine kinase, Ret, cause formation of tumors of neuroendocrine derivation in the multiple endocrine neoplasia type 2 and, thus, likely interfere with antiproliferative and/or differentiative extracellular signals. Here we took advantage of two rat pheochromocytoma-derived cell lines (PC12/MEN2A and PC12/MEN2B)...
Article
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Specific germline mutations of the receptor tyrosine kinase, Ret, predispose to multiple endocrine neoplasia types 2A and 2B and familial medullary thyroid carcinoma. The mechanisms by which different Ret isoforms (Ret-2A and Ret-2B) cause distinct neoplastic diseases remain largely unknown. On the other hand, forced expression of these mutated ver...
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Pheochromocytomas are tumors originating from chromaffin cells, the large majority of which are sporadic neoplasms. The genetic and molecular events determining their tumorigenesis continue to remain unknown. On the other hand, RET germ-line mutations cause the inheritance of familial tumors in multiple endocrine neoplasia (MEN)-2 diseases, which a...
Article
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A mes-c-myc A1 (A1) cell line was generated by retroviral infection of cultured embryonic mesencephalic cells and selected by neomycin resistance. A1 cells cease to divide and undergo morphological differentiation after serum withdrawal or addition of c-AMP. Proliferating or morphologically differentiated A1 cells are all positive for vimentin and...
Article
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Inherited activating mutations of Ret, a receptor tyrosine kinase, predispose to multiple endocrine neoplasia (MEN) types 2A and 2B and familial medullary thyroid carcinoma. To investigate the effects induced by acute stimulation of Ret, we transfected both PC12 and NIH 3T3 cells with a molecular construct in which the ligand-binding domain of the...
Article
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The product of the RET proto-oncogene is a protein belonging to the receptor-like tyrosine kinase superfamily. RET is expressed in several neural crest-derived cell lineages and has been implicated in the correct development of the peripheral nervous system. To gain further insight into RET function, we investigated the presence of active RET in ad...