Affiliations: [a] Department of Neuroscience, University of Torino, Torino, Italy
| [b] Neuroscience Institute Cavalieri Ottolenghi Foundation (NICO), University of Torino, Torino, Italy
| [c] École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
| [d] Department of Drug Science and Technology, University of Torino, Torino, Italy
| [e] Department of Internal Medicine and Medical Specialties (DIMI), Unit of Geriatric Medicine, University of Genova, Genova, Italy
| Location of work: University of Torino Neuroscience Institute of Cavalieri Ottolenghi Foundation (NICO), University of Torino, Torino, Italy.
Correspondence:
[*]
Correspondence to: Elena Tamagno, Neuroscience Institute Cavalieri Ottolenghi, University of Torino; Regione
Gonzole 10, 10043, Orbassano, Torino, Italy. Tel.: +39 0116706604; E-mail: E-mail: [email protected] and Massimo Tabaton, Department of Internal Medicine and Medical Specialties (DIMI), Viale Benedetto XV, 6,
16132, Genova, Italy. Tel./Fax: +39 0103537064; E-mail: E-mail: [email protected].
Abstract: Neuroinflammation is involved in the pathogenesis of Alzheimer’s disease, and the transcription factor NF-κB is a player in this event. We found here that the ischemic damage alone or in association with Aβ1-42 activates the NF-κB pathway, induces an increase of BACE1 and a parallel inhibition of Uch-L1 and TREM2, both in vitro and in vivo, in Tg 5XFAD and in human brains of sporadic AD. This mechanism creates a synergistic loop that fosters inflammation. We also demonstrated a significant protection exerted by the restoration of Uch-L1 activity. The rescue of the enzyme is able to abolish the decrease of TREM2 and the parameters of neuroinflammation.
