References of "Michelucci, Alessandro 50002670"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailMicroglial activation depends on beta-amyloid conformation: role of the formylpeptide receptor 2
Heurtaux, Tony UL; Michelucci, Alessandro UL; Losciuto, Sophie UL et al

in Journal of Neurochemistry (2010), 114(2), 576-586

Alzheimer's disease (AD) is characterized by the presence of extracellular deposits referred to beta-amyloid (Abeta) complexes or senile plaques. Abeta peptide is firstly produced as monomers, readily ... [more ▼]

Alzheimer's disease (AD) is characterized by the presence of extracellular deposits referred to beta-amyloid (Abeta) complexes or senile plaques. Abeta peptide is firstly produced as monomers, readily aggregating to form multimeric complexes, of which the smallest aggregates are known to be the most neurotoxic. In AD patients, abundant reactive microglia migrate to and surround the Abeta plaques. Though it is well known that microglia are activated by Abeta, little is known about the peptide conformation and the signaling cascades responsible for this activation. In this study, we have stimulated murine microglia with different Abeta(1-42) forms, inducing an inflammatory state, which was peptide conformation-dependent. The lightest oligomeric forms induced a more violent inflammatory response, whereas the heaviest oligomers and the fibrillar conformation were less potent inducers. BocMLF, a formylpeptide chemotactic receptor 2 antagonist, decreased the oligomeric Abeta-induced inflammatory response. The Abeta-induced signal transduction was found to depend on phosphorylation mechanisms mediated by MAPKs and on activator protein 1/nuclear factor kappa-light-chain-enhancer of activated B cells pathways activation. These results suggest that the reactive microgliosis intensity during AD might depend on the disease progression and consequently on the Abeta conformation production. The recognition of Abeta by the formylpeptide chemotactic receptor 2 seems to be a starting point of the signaling cascade inducing an inflammatory state. [less ▲]

Detailed reference viewed: 188 (43 UL)
Full Text
Peer Reviewed
See detailCharacterization of the microglial phenotype under specific pro-inflammatory and anti-inflammatory conditions: Effects of oligomeric and fibrillar amyloid-beta
Michelucci, Alessandro UL; Heurtaux, Tony UL; Grandbarbe, Luc UL et al

in Journal of Neuroimmunology (2009), 210(1-2), 3-12

M1 and M2 are the extremes of the differentiation spectrum of activated macrophages. Since microglia are members of the same cell lineage, we have characterized their transcription profile and their ... [more ▼]

M1 and M2 are the extremes of the differentiation spectrum of activated macrophages. Since microglia are members of the same cell lineage, we have characterized their transcription profile and their phagocytic activity under different conditions. LPS or IFN-gamma induce a M1-like phenotype, while IL-10 or IL-4 differentiate microglia towards a M2-deactivated or M2-alternatively-activated phenotype respectively. These differentiation processes also affect the Notch pathway. In order to study the polarization induced by Abeta, microglia was stimulated with different forms of the peptide. The oligomeric Abeta is a stronger M1-inductor than the fibrillar form. Moreover, a cytokine-induced anti-inflammatory environment reduces the microglial reactivity towards oligomeric Abeta. [less ▲]

Detailed reference viewed: 66 (5 UL)
Full Text
Peer Reviewed
See detailDual bioactivity of resveratrol fatty alcohols: differentiation of neural stem cells and modulation of neuroinflammation
Hauss, Frederique; Liu, Jiawei; Michelucci, Alessandro UL et al

in Bioorganic & Medicinal Chemistry Letters (2007), 17(15), 4218-4222

The synthesis of resveratrol fatty alcohols (RFAs), a new class of small molecules presenting strong potential for the treatment of neurological diseases, is described. RFAs, hybrid compounds combining ... [more ▼]

The synthesis of resveratrol fatty alcohols (RFAs), a new class of small molecules presenting strong potential for the treatment of neurological diseases, is described. RFAs, hybrid compounds combining the resveratrol nucleus and omega-alkanol side chains, are able to modulate neuroinflammation and to induce differentiation of neural stem cells into mature neurons. Acting on neuroprotection and neuroregeneration, RFAs represent an innovative approach for the treatment or cure of neuropathies. [less ▲]

Detailed reference viewed: 111 (2 UL)
Full Text
Peer Reviewed
See detailNotch signaling modulates the activation of microglial cells
Grandbarbe, Luc UL; Michelucci, Alessandro UL; Heurtaux, Tony UL et al

in Glia (2007), 55(15), 1519-30

The Notch signaling pathway plays a crucial role in specifying cellular fate in metazoan development by regulating communication between adjacent cells. Correlative studies suggested an involvement of ... [more ▼]

The Notch signaling pathway plays a crucial role in specifying cellular fate in metazoan development by regulating communication between adjacent cells. Correlative studies suggested an involvement of Notch in hematopoietic cell development. Here, we report that the Notch pathway is expressed and active in microglial cells. During inflammatory activation, the transcription of the Notch down-stream effector Hes1 is downregulated. When Notch1 transcription in microglia is inhibited, an upregulation of the expression of pro-inflammatory cytokines is observed. Notch stimulation in activated microglia, using a soluble form of its ligand Jagged1, induces a decrease in pro-inflammatory cytokines secretion and nitric oxide production as well as an increase in phagocytic activity. Notch-stimulation is accompanied by an increase in the rate of STAT3 phosphorylation and nuclear translocation. Our results show that the Notch pathway plays an important role in the control of inflammatory reactions in the CNS. [less ▲]

Detailed reference viewed: 160 (6 UL)