Micro RNA-137/181c regulates serine palmitoyltransferase and in turn amyloid β novel targets in sporadic Alzheimer's disease

Hirosha Geekiyanage, Christina Chan

Research output: Contribution to journalArticle

  • 128 Citations

Abstract

The contribution of mutations in amyloid precursor protein (APP) and presenilin (PSEN) to familial Alzheimer's disease (AD) is well established. However, little is known about the molecular mechanisms leading to amyloidβ (Aβ) generation in sporadic AD. Increased brain ceramide levels have been associated with sporadic AD, and are a suggested risk factor. Serine palmitoyltransferase (SPT) is the first rate-limiting enzyme in the de novo ceramide synthesis. However, the regulation of SPT is not yet understood. Evidence suggests that it may be posttranscriptionally regulated. Therefore, we investigated the role of miRNAs in the regulation of SPT and amyloid β (Aβ) generation. We show that SPT is upregulated in a subgroup of sporadic AD patient brains. This is further confirmed in mouse model studies of risk factors associated with AD. We identified that the loss of miR-137, -181c, -9, and 29a/b-1 increases SPT and in turn Aβ levels, and provides a mechanism for the elevated risk of ADassociated with age, high-saturated-fat diet, and gender. Finally, these results suggest SPT and the respective miRNAs may be potential therapeutic targets for sporadic AD.

LanguageEnglish (US)
Pages14820-14830
Number of pages11
JournalJournal of Neuroscience
Volume31
Issue number41
DOIs
StatePublished - Oct 12 2011

Profile

Serine C-Palmitoyltransferase
MicroRNAs
Amyloid
Alzheimer Disease
Ceramides
Presenilins
Amyloid beta-Protein Precursor
Brain
High Fat Diet
Mutation
Enzymes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Micro RNA-137/181c regulates serine palmitoyltransferase and in turn amyloid β novel targets in sporadic Alzheimer's disease. / Geekiyanage, Hirosha; Chan, Christina.

In: Journal of Neuroscience, Vol. 31, No. 41, 12.10.2011, p. 14820-14830.

Research output: Contribution to journalArticle

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