WORK PACKAGE 1

Basic mechanisms of microglia activation and new molecular targets

Twelve INMiND partner institutions from eight countries (Austria, Belgium, Denmark, Germany, Hungary, Italy, Spain, United Kingdom) are involved in the research activities of this work package. Leader of this work package is Adriana MAGGI, head of the Centre of Excellence on Neurodegenerative Diseases (CEND) at the University of Milano (Italy).

The main objectives of this work package are:

  • to study basic mechanisms of microglial activation and the identification of candidate markers for M1/M2 switch
  • to characterize microglial activation and function in ND and define molecular targets to enable development of new molecules (=>WP3) as imaging biomarkers for NIND which may also serve as targets for NIND therapy
  • to generate innovative animal models for in vivo imaging of microglial activation phenotypes
  • to define the role of gender in NI and ND

WP1 Related papers


Epub ahead of print

Maggi A, Della Torre S. Sex, metabolism and health. Mol Metab. 2018 Feb 27. pii: S2212-8778(18)30037-1; epub ahead of print.
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2018

Rizzi N, Villa A, Benedusi V, Brunialti E, Cesari N, Ciana P, Maggi A. Endocrine influence on neuroinflammation: the use of reporter systems. J Neuroendocrinol. 2017; epub ahead of print.
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Villa A, Gelosa P, Castiglioni L, Cimino M, Rizzi N, Pepe G, Lolli F, Marcello E, Sironi L, Vegeto E, Maggi A. Sex-Specific Features of Microglia from Adult Mice. Cell Rep. 2018;23(12):3501-3511.
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2017

Benedusi V, Della Torre S, Mitro N, Caruso D, Oberto A, Tronel C, Meda C, Maggi A. Liver ERα regulates AgRP neuronal activity in the arcuate nucleus of female mice. Sci Rep. 2017;7(1):1194.
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Bonfill-Teixidor E, Otxoa-de-Amezaga A, Font-Nieves M, Sans-Fons MG, Planas AM. Differential expression of E-type prostanoid receptors 2 and 4 in microglia stimulated with lipopolysaccharide. J Neuroinflammation. 2017;14(1):3.
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Bozó T, Wacha A, Mihály J, Bóta A, Kellermayer MS. Dispersion and stabilization of cochleate nanoparticles. Eur J Pharm Biopharm. 2017;117:270-275.
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Brufani M, Rizzi N, Meda C, Filocamo L, Ceccacci F, D’Aiuto V, Bartoli G, La Bella A, Migneco LM, Marini Bettolo R, Leonelli F, Ciana P, Maggi A. Novel Locally Active Estrogens Accelerate Cutaneous Wound Healing-Part 2. Sci Rep. 2017;7(1):2510.
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Della Torre S, Maggi A. Sex Differences: A Resultant of an Evolutionary Pressure? Cell Metabolism 2017; 25(3):499–505.
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Lepelletier FX, Mann DM, Robinson AC, Pinteaux E, Boutin H. Early changes in extracellular matrix in Alzheimer's disease. Neuropathol Appl Neurobiol. 2017;43(2):167-182.
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Mártonfalvi Z, Bianco P, Naftz K, Ferenczy GG, Kellermayer M. Force generation by titin folding. Protein Sci. 2017;26(7):1380-1390.
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Nguyen HM, Blomster LV, Christophersen P, Wulff H. Potassium channel expression and function in microglia: Plasticity and possible species variations. Channels (Austin). 2017;11(4):305-315.
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Pepe G, Braga D, Renzi TA, Villa A, Bolego C, D’Avila F, Barlassina C, Maggi A, Locati M, Vegeto E. Self-renewal and phenotypic conversion are the main physiological responses of macrophages to the endogenous estrogen surge. Scientific Reports 7: 44270.
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Pepe G, De Maglie M, Minoli L, Villa A, Maggi A, Vegeto E. Selective proliferative response of microglia to alternative polarization signals. J Neuroinflammation. 2017;14(1):236.
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Pires RH, Saraiva MJ, Damas AM, Kellermayer MS. Force spectroscopy reveals the presence of structurally modified dimers in transthyretin amyloid annular oligomers. J Mol Recognit. 2017;30(3).
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Rizzi N, Rebecchi M, Levandis G, Ciana P, Maggi A. Identification of novel loci for the generation of reporter mice. Nucleic Acids Res 2017;45(6):e37.
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2016

Blomster LV, Strøbæk D, Christophersen PC. Detection of pro-inflammatory ion channel activity in human microglia, the brain macrophages. BioZoom 2016;18(1):14-16.
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Blomster LV, Strøbæk D, Hougaard C, Klein J, Pinborg L, Mikkelsen JD, Christophersen P. Quantification of the functional expression of the Ca2+-activated K+ channel KCa3.1 on microglia from adult human neocortical tissue. Glia. 2016;64(12):2065-2078.
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Bozó T, Mészáros T, Mihály J, Bóta A, Kellermayer MS, Szebeni J, Kálmán B. Aggregation of PEGylated liposomes driven by hydrophobic forces. Colloids Surf B Biointerfaces. 2016;147:467-74.
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Macchi F, Deleersnijder A, Van den Haute C, Munck S, Pottel H, Michiels A, Debyser Z, Gerard M, Baekelandt V. High-content analysis of α-synuclein aggregation and cell death in a cellular model of Parkinson's disease. J Neurosci Methods. 2016;261:117-27.
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Van der Perren A, Casteels C, Van Laere K, Gijsbers R, Van Den Haute C, Baekelandt V. Development of an alpha-synuclein based rat model for Parkinson’s Disease via stereotactic injection of a recombinant adeno-associated viral vector. J Vis Exp. 2016;(108):53670.
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Villa A, Vegeto E, Poletti A, Maggi A. Estrogens, neuroinflammation and neurodegeneration. Endocr Rev. 2016;37(4):372-402.
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2015

Benedusi V, Martini E, Kallikourdis M, Villa A, Meda C, Maggi A. Ovariectomy shortens the life span of female mice. Oncotarget. 2015;6(13):10801-11.
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Bentea E, Van der Perren A, Van Liefferinge J, El Arfani A, Albertini G, Demuyser T, Merckx E, Michotte Y, Smolders I, Baekelandt V, Massie A. Nigral proteasome inhibition in mice leads to motor and non-motor deficits and increased expression of Ser129 phosphorylated α-synuclein. Front Behav Neurosci. 2015;9:68.
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Bianco P, Mártonfalvi Z, Naftz K, Kőszegi D, Kellermayer M. Titin domains progressively unfolded by force are homogenously distributed along the molecule. Biophys J. 2015;109(2):340-5.
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Bozó T, Brecska R, Gróf P, Kellermayer MS. Extreme resilience in cochleate nanoparticles. Langmuir. 2015;31(2):839-45.
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Farde L. Spotlight: TSPO binding may also represent ‘resting’ microglia. Clin Transl Imaging. 2015;3(6):491-492.
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Janssens K, Maheshwari A, Van Den Haute C, Baekelandt V, Stinissen P, Hendriks J, Slaets H, Hellings N. Oncostatin M protects against demyelination by inducing a protective microglial phenotype. Glia. 2015;63(10):1729-37.
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Krauthausen M, Kummer MP, Zimmermann J, Reyes-Irisarri E, Terwel D, Bulic B, Heneka MT, Müller M. CXCR3 promotes plaque formation and behavioral deficits in an Alzheimer's disease model. J Clin Invest. 2015;125(1):365-78.
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Kummer MP, Schwarzenberger R, Sayah-Jeanne S, Dubernet M, Walczak R, Hum DW, Schwartz S, Axt D, Heneka MT. Pan-PPAR modulation effectively protects APP/PS1 mice from amyloid deposition and cognitive deficits. Mol Neurobiol. 2015;51(2):661-71.
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Murvai Ü, Somkuti J, Smeller L, Penke B, Kellermayer MS. Structural and nanomechanical comparison of epitaxially and solution-grown amyloid β25-35 fibrils. Biochim Biophys Acta-Proteins and Proteomics. 2015;1854(5):327-32.
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Villa A, Rizzi N, Vegeto E, Ciana P, Maggi A. Estrogen accelerates the resolution of inflammation in macrophagic cells. Estrogen accelerates the resolution of inflammation in macrophagic cells. Sci Rep. 2015;5:15224.
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2014

Brosseron F, Krauthausen M, Kummer M, Heneka MT. Body fluid cytokine levels in mild cognitive impairment and Alzeimer's disease: a comparative overview. Mol Neurobiol. 2014;50(2):534-44.
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Cunha L, Szigeti K, Mathé D, Metello LF. The role of molecular imaging in modern drug development. Drug Discov Today. 2014;19(7):936-48.
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Della Torre S, Benedusi V, Fontana R, Maggi A. Energy metabolism and fertility - a balance preserved for female health. Nat Rev Endocrinol. 2014;10(1):13-23.
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Kummer MP, Hammerschmidt T, Martinez A, Terwel D, Eichele G, Witten A, Figura S, Stoll M, Schwartz S, Pape HC, Schultze JL, Weinshenker D, Heneka MT. Ear2 deletion causes early memory and learning deficits in APP/PS1 mice. J Neurosci. 2014;34(26):8845-54.
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Kummer MP, Heneka MT. Truncated and modified amyloid-beta species. Alzheimers Res Ther. 2014;6(3):28.
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Maggi A, Villa A. In vivo dynamics of estrogen receptor activity: The ERE-Luc model. J Steroid Biochem Mol Biol. 2014;139:262-9.
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Mártonfalvi Z, Bianco P, Linari M, Caremani M, Nagy A, Lombardi V, Kellermayer M. Low-force transitions in single titin molecules reflect a memory of contractile history. J Cell Sci. 2014;127(Pt 4):858-870.
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Mártonfalvi Z, Kellermayer M. Individual globular domains and domain unfolding visualized in overstretched titin molecules with atomic force microscopy. PLoS One. 2014;9(1):e85847.
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Pepe G, Calderazzi G, De Maglie M, Villa A, Vegeto E. Heterogeneous induction of microglia M2a phenotype by central administration of interleukin-4. J Neuroinflammation. 2014;11(1):1031.
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2013

Kellermayer M, Murvai Ü, Horváth A, Lászlóffi E, Soós K, Penke B. Epitaxial assembly dynamics of mutant amyloid β25–35_N27C fibrils explored with time-resolved scanning force microscopy. Biophysical Chemistry. 2013;184C:54-61.
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2012

Abourbeh G, Thézé B, Maroy R, Dubois A, Brulon V, Fontyn Y, Dollé F, Tavitian B, Boisgard R. Imaging microglial/macrophage activation in spinal cords of experimental autoimmune encephalomyelitis rats by positron emission tomography using the mitochondrial 18 kDa translocator protein radioligand [¹⁸F]DPA-714. J Neurosci. 2012;32(17):5728-36.
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Agócs G, Szabó BT, Köhler G, Osváth S. Comparing the folding and misfolding energy landscapes of phosphoglycerate kinase. Biophys J. 2012;102(12):2828-34.
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Benedusi V, Martorana F, Brambilla L, Maggi A, Rossi D. The peroxisome proliferator-activated receptor γ (PPARγ) controls natural protective mechanisms against lipid peroxidation in amyotrophic lateral sclerosis. J Biol Chem. 2012;287(43):35899-911.
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Jacobs AH, Tavitian B; INMiND consortium. Noninvasive molecular imaging of neuroinflammation. J Cereb Blood Flow Metab. 2012;32(7):1393-415.
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