First Author | Geekiyanage H | Year | 2013 |
Journal | Neurobiol Aging | Volume | 34 |
Issue | 8 | Pages | 2037-51 |
PubMed ID | 23528227 | Mgi Jnum | J:211741 |
Mgi Id | MGI:5576107 | Doi | 10.1016/j.neurobiolaging.2013.02.001 |
Citation | Geekiyanage H, et al. (2013) Inhibition of serine palmitoyltransferase reduces Abeta and tau hyperphosphorylation in a murine model: a safe therapeutic strategy for Alzheimer's disease. Neurobiol Aging 34(8):2037-51 |
abstractText | The contribution of the autosomal dominant mutations to the etiology of familial Alzheimer's disease (AD) is well characterized. However, the molecular mechanisms contributing to sporadic AD are less well understood. Increased ceramide levels have been evident in AD patients. We previously reported that increased ceramide levels, regulated by increased serine palmitoyltransferase (SPT), directly mediate amyloid beta (Abeta) levels. Therefore, we inhibited SPT in an AD mouse model (TgCRND8) through subcutaneous administration of L-cylcoserine. The cortical Abeta(4)(2) and hyperphosphorylated tau levels were down-regulated with the inhibition of SPT/ceramide. Positive correlations were observed among cortical SPT, ceramide, and Abeta(4)(2) levels. With no evident toxic effects observed, inhibition of SPT could be a safe therapeutic strategy to ameliorate the AD pathology. We previously observed that miR-137, -181c, -9, and 29a/b post-transcriptionally regulate SPT levels, and the corresponding miRNA levels in the blood sera are potential diagnostic biomarkers for AD. Here, we observe a negative correlation between cortical Abeta(4)(2) and sera Abeta(4)(2), and a positive correlation between cortical miRNA levels and sera miRNA levels suggesting their potential as noninvasive diagnostic biomarkers. |