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1

INSERM U930, Université François Rabelais de Tours, 10 boulevard Tonnelé, 37032 Tours, France

2

CHRU de Tours, 37044 Tours, France





*

Author to whom correspondence should be addressed.



Academic Editors: Styliani-Anna E. Tsirka and Jillian Nissen

Abstract Microglia, as cellular mediators of neuroinflammation, are implicated in the pathogenesis of a wide range of neurodegenerative diseases. Positron emission tomography PET imaging of microglia has matured over the last 20 years, through the development of radiopharmaceuticals targeting several molecular biomarkers of microglial activation and, among these, mainly the translocator protein-18 kDa TSPO. Nevertheless, current limitations of TSPO as a PET microglial biomarker exist, such as low brain density, even in a neurodegenerative setting, expression by other cells than the microglia astrocytes, peripheral macrophages in the case of blood brain barrier breakdown, genetic polymorphism, inducing a variation for most of TSPO PET radiopharmaceuticals’ binding affinity, or similar expression in activated microglia regardless of its polarization pro- or anti-inflammatory state, and these limitations narrow its potential interest. We overview alternative molecular targets, for which dedicated radiopharmaceuticals have been proposed, including receptors purinergic receptors P2X7, cannabinoid receptors, α7 and α4β2 nicotinic acetylcholine receptors, adenosine 2A receptor, folate receptor β and enzymes cyclooxygenase, nitric oxide synthase, matrix metalloproteinase, β-glucuronidase, and enzymes of the kynurenine pathway, with a particular focus on their respective contribution for the understanding of microglial involvement in neurodegenerative diseases. We discuss opportunities for these potential molecular targets for PET imaging regarding their selectivity for microglia expression and polarization, in relation to the mechanisms by which microglia actively participate in both toxic and neuroprotective actions in brain diseases, and then take into account current clinicians’ expectations. View Full-Text

Keywords: microglial activation; neuroinflammation; PET; biomarker; neurodegenerative disorders microglial activation; neuroinflammation; PET; biomarker; neurodegenerative disorders





Autor: Claire Tronel 1,* , Bérenger Largeau 2, Maria Joao Santiago Ribeiro 1,2, Denis Guilloteau 1,2, Anne-Claire Dupont 1,2 and Nicolas Arlicot 1,2

Fuente: http://mdpi.com/



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