Stroke and Amyloid-β 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-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.

• Publication year

  2019

• Venue

  Journal of Alzheimer's Disease

• Publication date

  2019-08-21

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3233/JAD-190494PMID 31450501
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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