Current paradigm of the 18-kDa translocator protein (TSPO) as a molecular target for PET imaging in neuroinflammation and neurodegenerative diseases

Neuroinflammation is a process characterised by drastic changes in microglial morphology and by marked upregulation of the 18-kDa translocator protein (TSPO) on the mitochondria. The continual increase in incidence of neuroinflammation and neurodegenerative diseases poses a major health issue in many countries, requiring more innovative diagnostic and monitoring tools. TSPO expression may constitute a biomarker for brain inflammation that could be monitored by using TSPO tracers as neuroimaging agents. From medical imaging perspectives, this review focuses on the current concepts related to the TSPO, and discusses briefly on the status of its PET imaging related to neuroinflammation and neurodegenerative diseases in humans

Approche synthétique de l'Erinacine A, diterpène de la famille des cyathines, activateur de la biosynthèse du facteur de croissance nerveuse

Les cyathines forment une famille de diterpènes naturels présentant un squelette tricyclique décahydro- 2H-cyclohepta[e]indène unique parmi les terpènes. Ces composés sont capables de stimuler la production endogène du facteur de croissance nerveuse et par conséquent pourraient être employés dans le traitement des maladies nerveuses dégénératives comme la maladie d'Alzeihmer. Dans ce travail, nous décrivons une nouvelle voie d'accès à cette classe de molécules, selon une stratégie dans laquelle le cycle C à 7 chaînons est élaboré par une réaction d'homologation de cycle à partir d'un système décahydro-2H-cyclopenta[a]naphtalène. L'étape clé de la synthèse est la construction du cycle B par une réaction tandem Heck/Tsuji-Trost, qui permet un parfait contrôle de la relation stéréochimique anti entre les deux groupements angulaires...Cyathins are diterpenoid natural products which display an unusual tricyclic decahydro-2H-cyclohepta[e]indene skeleton. These compounds are strong stimulators of nerve growth factor synthesis and have been expected as medicine for degenerative neuronal disorders such as Alzeihmer's disease. The present work describes a new access to these compounds according to a strategy in which the tricyclic [ABC] core is produced from a decahydro-2H-cyclopenta[a]naphthalene by a one-carbon expansion reaction of the six-membered C-ring. The key step of the synthesis is the formation of the ring B through a Heck-acetate ion capture reaction in which the crucial control of the anti configuration between the rings A and C was achieved with a high selectivity. The absolute configuration of the A-subunit containing the stereo-defined C-9 angular methyl group was controlled by using the deracemizing Michael addition involving the chiral imine derived from 1-methylcyclopentanone and (s)-1-phenylethylamine.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF