FEDERICA ARMELI

Dottoressa di ricerca

ciclo: XXXV



Titolo della tesi: URB597 Administration decreases Neuroinflammation and promotes Autophagy in Alzheimer's Disease models

In recent years, much attention has been focused on the endocannabinoid system as a therapeutic target for neurodegenerative diseases, including Alzheimer's disease (AD). The first endocannabinoid to be characterized was anandamide (N -arachidonoyl ethanolamine, AEA), which is hydrolyzed in postsynaptic neurons by the fatty acid amide hydrolase (FAAH). Notably, the post-mortem examination of brains from AD patients has revealed several alterations of the endocannabinoid system reporting a decrease in cortical AEA levels and a parallel increase in FAAH activity. On this ground, by using both cellular and a transgenic mouse model of AD, we aimed at determining whether pharmacological inhibition of FAAH via URB597 administration may affect microglia polarization and provide beneficial effects in restoring autophagic process and reducing amyloid-β (Aβ) aggregates, which are all neuropathological features of AD. The evaluation of morphological and major markers of microglial activation (iNOS and ARG-1) showed the ability of URB597 to revert microglial activation towards an anti-inflammatory condition, which was associated with the decrease of pro-inflammatory cytokines and an increase of anti-inflammatory cytokines together with the restoration of key factors involved in autophagic processes. These data were confirmed in vivo in the Tg2576 mice where the broad-spectrum action of endocannabinoids ranging from the anti-inflammatory action to the restoration of autophagic flux was demonstrated by the increase of proteins such as ATG7, Beclin1, LC3 and activation of ULK1 signaling following mTOR decrease after URB597 treatment. Moreover, treatment with URB597 decreases the expression of BACE1 through the modulation of CB2 receptors, leading to the reduction of amyloid plaques. Taken together, these data suggest that inhibition of FAAH can drive the polarization of microglia towards an anti-inflammatory phenotype and demonstrate that the modulation of the endocannabinoid system in AD, via URB597 administration, could be a potential and effective therapy not only to fight neuroinflammation but also to regulate the autophagic machinery.

Produzione scientifica

11573/1685529 - 2023 - Perinatal S-Adenosylmethionine Supplementation Represses PSEN1 Expression by the Cellular Epigenetic Memory of CpG and Non-CpG Methylation in Adult TgCRD8 Mice
Raia, Tiziana; Armeli, Federica; Cavallaro, Rosaria A.; Ferraguti, Giampiero; Businaro, Rita; Lucarelli, Marco; Fuso, Andrea - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. - - issn: 1422-0067 - wos: WOS:001038740600001 (1) - scopus: 2-s2.0-85166017123 (0)

11573/1674647 - 2023 - A multimethodological approach for the valorization of “Senatore Cappelli” wheat milling by-products as a source of bioactive compounds and nutraceutical activity
Vinci, Giuliana; Prencipe, Sabrina Antonia; Armeli, Federica; Businaro, Rita - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH (Basel: MDPI 2003-) pp. 1-22 - issn: 1660-4601 - wos: (0) - scopus: 2-s2.0-85151109500 (0)

11573/1664474 - 2022 - Milmed yeast alters the LPS-induced M1 microglia cells to Form M2 anti-inflammatory phenotype
Armeli, Federica; Mengoni, Beatrice; Maggi, Elisa; Mazzoni, Cristina; Preziosi, Adele; Mancini, Patrizia; Businaro, Rita; Lenz, Thomas; Archer, Trevor Cornelius Stuart - 01a Articolo in rivista
rivista: BIOMEDICINES (Basel : MDPI) pp. - - issn: 2227-9059 - wos: WOS:000900498300001 (2) - scopus: 2-s2.0-85144730353 (3)

11573/1637151 - 2022 - Milmed saccharomyces cerevisiae activity on central nervous system cells
Maggi, E; Armeli, F; Mengoni, B; Leo, M; Filetici, P; Mancini, P; Lenz, T; Businaro, R; And Archer, T - 01a Articolo in rivista
rivista: JOURNAL OF TOXICOLOGY AND PHARMACOLOGY (Hyderabad, Telangana, India: Scientific Open Access Journals (SOAJ)) pp. 1-8 - issn: - wos: (0) - scopus: (0)

11573/1553131 - 2021 - Mediterranean diet and neurodegenerative diseases: the neglected role of nutrition in the modulation of the endocannabinoid system
Armeli, Federica; Bonucci, Alessio; Maggi, Elisa; Pinto, Alessandro; Businaro, Rita - 01g Articolo di rassegna (Review)
rivista: BIOMOLECULES (Basel: MDPI) pp. - - issn: 2218-273X - wos: WOS:000665287600001 (10) - scopus: 2-s2.0-85106209935 (13)

11573/1570251 - 2021 - Fatty acid amide hydrolase (Faah) inhibition modulates amyloid-beta-induced microglia polarization
Grieco, M.; De Caris, M. G.; Maggi, E.; Armeli, F.; Coccurello, R.; Bisogno, T.; D'erme, M.; Maccarrone, M.; Mancini, P.; Businaro, R. - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel: MDPI Center) pp. - - issn: 1422-0067 - wos: WOS:000676716400001 (17) - scopus: 2-s2.0-85110728853 (18)

11573/1452187 - 2020 - Nutraceuticals as potential therapeutics for vesicant-induced pulmonary fibrosis
Businaro, Rita; Maggi, Elisa; Armeli, Federica; Murray, Alexa; Laskin, Debra L - 01g Articolo di rassegna (Review)
rivista: ANNALS OF THE NEW YORK ACADEMY OF SCIENCES (New York: New York Academy of Sciences) pp. 1-9 - issn: 0077-8923 - wos: WOS:000553062000001 (1) - scopus: 2-s2.0-85097112497 (1)

11573/1454829 - 2020 - Blueberry counteracts bv-2 microglia morphological and functional switch after lps challenge
De Caris, M. G.; Grieco, M.; Maggi, E.; Francioso, A.; Armeli, F.; Mosca, L.; Pinto, A.; D'erme, M.; Mancini, P.; Businaro, R. - 01a Articolo in rivista
rivista: NUTRIENTS (Basel, Switzerland: Molecular Diversity Preservation International (MDPI)) pp. 1-18 - issn: 2072-6643 - wos: WOS:000549236200001 (16) - scopus: 2-s2.0-85087021023 (17)

11573/1436010 - 2020 - Immunohistochemical detection of IL-17 and IL-23 improves the identification of patients with a possible diagnosis of Sjogren's syndrome
Fusconi, M; Musy, I; Valente, D; Maggi, E; Priori, R; Pecorella, I; Mastromanno, L; Di Cristofano, C; Greco, A; Armeli, F; Candelori, F; De Vincentiis, M; Gallo, A; Businaro, R. - 01a Articolo in rivista
rivista: PATHOLOGY RESEARCH AND PRACTICE (Urban & Fischer Verlag Jena:Postfach 100537, D-07705 Jena Germany:011 49 3641 626430, EMAIL: journals@urbanfischer.de, INTERNET: http://www.urbanfischer.de, Fax: 011 49 3641 626500) pp. - - issn: 0344-0338 - wos: WOS:000587606400015 (6) - scopus: 2-s2.0-85090035524 (6)

11573/1392856 - 2020 - Relationship between proinflammatory cytokines (Il-1beta, Il-18) and leukocyte telomere length in mild cognitive impairment and Alzheimer's disease
Scarabino, D.; Peconi, M.; Broggio, E.; Gambina, G.; Maggi, E.; Armeli, F.; Mantuano, E.; Morello, M.; Corbo, R. M.; Businaro, R. - 01a Articolo in rivista
rivista: EXPERIMENTAL GERONTOLOGY (PERGAMON-ELSEVIER SCIENCE LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND, OX5 1GB) pp. - - issn: 0531-5565 - wos: WOS:000538049900001 (24) - scopus: 2-s2.0-85083208621 (25)

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