Skip to Content
Merck
  • Palmitate induces transcriptional regulation of BACE1 and presenilin by STAT3 in neurons mediated by astrocytes.

Palmitate induces transcriptional regulation of BACE1 and presenilin by STAT3 in neurons mediated by astrocytes.

Experimental neurology (2013-08-24)
Li Liu, Rebecca Martin, Garrett Kohler, Christina Chan
ABSTRACT

Deregulation of calcium has been implicated in neurodegenerative diseases, including Alzheimer's disease (AD). Previously, we showed that saturated free-fatty acid, palmitate, causes AD-like changes in primary cortical neurons mediated by astrocytes. However, the molecular mechanisms by which conditioned medium from astrocytes cultured in palmitate induce AD-like changes in neurons are unknown. This study demonstrates that this condition medium from astrocytes elevates calcium level in the neurons, which subsequently increases calpain activity, a calcium-dependent protease, leading to enhance p25/Cdk5 activity and phosphorylation and activation of the STAT3 (signal transducer and activator of transcription) transcription factor. Inhibiting calpain or Cdk5 significantly reduces the upregulation in nuclear level of pSTAT3, which we found to transcriptionally regulate both BACE1 and presenilin-1, the latter is a catalytic subunit of γ-secretase. Decreasing pSTAT3 levels reduced the mRNA levels of both BACE1 and presenilin-1 to near control levels. These data demonstrate a signal pathway leading to the activation of STAT3, and the generation of the amyloid peptide. Thus, our results suggest that STAT3 is an important potential therapeutic target of AD pathogenesis.

MATERIALS
Product Number
Brand
Product Description

Palmitic acid, European Pharmacopoeia (EP) Reference Standard
Supelco
Palmitic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Palmitic acid, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Sigma-Aldrich
Palmitic acid, natural, 98%, FG
Sigma-Aldrich
Palmitic acid, BioXtra, ≥99%
Sigma-Aldrich
Roscovitine, ≥98% (TLC)
Supelco
Palmitic acid, analytical standard
Sigma-Aldrich
Palmitic acid, ≥98% palmitic acid basis (GC)
Sigma-Aldrich
Palmitic acid, ≥98%, FCC, FG
Sigma-Aldrich
Palmitic acid, ≥99%
Sigma-Aldrich
Anti-Spectrin alpha chain (nonerythroid) Antibody, clone AA6, clone AA6, Chemicon®, from mouse