Stroke and Amyloid-beta Downregulate TREM-2 and Uch-L1 Expression that Synergistically Promote the Inflammatory Response

Neuroinflammation is involved in the pathogenesis of Alzheimer's disease, and the transcription factor NF-kappa B is a player in this event. We found here that the ischemic damage alone or in association with A beta(1-42) activates the NF-kappa B 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.


Published in:
Journal of Alzheimers Disease, 71, 3, 907-920
Year:
Jan 01 2019
ISSN:
1387-2877
1875-8908
Keywords:
Laboratories:




 Record created 2019-10-18, last modified 2019-12-05


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