Table 1.
The regulatory molecules that are known to modulate the ADE level and or activity
| ADEs | Regulator | Effects | References |
|---|---|---|---|
|
| |||
| Neprilysin (NEP) | Somatostatin | Upregulation of NEP activity in primary cortical neurons | Saito et al., 2005 |
| Minocycline | Prevention of toxic effects of Aβ (25-35) by enhancing NEP expression in rat temporal cortex | Burgos-Ramos et al., 2009b | |
| Intracellular domain of APP and APLP (AICD) | Upregulation of NEP expression by AICD | Pardossi-Piquard et al., 2005 | |
| Gleevec (Tyrosine kinase inhibitor) | Elevation of NEP mRNA and protein levels | Eisele et al., 2007 | |
| Valproate and trichostatin A (Histone deacetylase inhibitors) | Increase in NEP expression and activity in SHSY-5Y cell | Belyaev et al., 2009 | |
| Estrogen | Regulation of NEP expression through physical interactions between estrogen receptor and estrogen response elements in the NEP gene | Xiao et al., 2009; Liang et al., 2010 | |
| Ginsenoside Rg3 | Promotion of Aβ degradation by enhancing gene expression of NEP | Yang et al., 2009 | |
| Green tea extract (EFLA®85942) | Strong enhancement of cellular NEP activity without change of cellular ACE activity | Melzig and Janka, 2003 | |
| GW742 (Selective PPARδ agonist) | Upregulation of NEP in 5xFAD mice | Kalinin et al., 2009 | |
| Polyphenols (Epilobium angustifolium) | Induction of NEP activity in SK-N-SH and PC-3 cells | Kiss et al., 2006 | |
| sICAM-1 | Induction of NEP expression in BV2 cells and in wild-type mice brains Decrease of Aβ plaques by hUCB-MSC-derived sICAM-1 which induces NEP expression in microglia | Kim et al., 2012 | |
| Erythropoietin | Enhanced metabolism of Aβ in MSCs by increasing their NEP content | Danielyan et al., 2009 | |
| Endothelin-converting enzyme (ECE-1) | PKCε | Promotion of Aβ clearance and reduction of AD neuropathology through increased ECE enzyme activity | Choi et al., 2006; Kim et al. 2011b |
| 4-hydroxy-nonenal (HNE) | Upregulation of ECE-1 mRNA and protein | Wang et al., 2009a, b | |
| Aβ | Elevation of endothelin-1 in AD and upregulated by Aβ | Palmer et al., 2012 | |
| Insulin degrading enzyme (IDE) | Retinoic acid | Upregulation by retinoic acid, a well-known inducer of neuronal differentiation and/or programmed cell death | Melino et al., 1996 |
| PPARγ | Activation of an IDE like Aβ degrading activity | Espuny-Camacho et al., 2010 | |
| HES-1 and Hey-1 (Notch signaling proteins) | Binding to IDE proximal promoter and repression of transcription and its activity | Leal et al., 2012 | |
| U0126 (ERK1/2 inhibitor) | Blocking of increased IDE protein level induced by fAβ | Leal et al., 2006 | |
| Angiotensin converting enzyme (ACE) | Perindopril (ACE inhibitor) | Cognitive impairment and brain injury in a mouse model of AD induced by intracerebroventricular injection of Aβ | Dong et al., 2011 |
| MMP-2 | Aβ | Enhancement of MMP-2 and membrane-type-MMP expression in U87 human glioma cell | Deb et al., 1999 |
| MMP-3 (Stromelysin-1) | Aβ | Increase of MMP-3 in enriched astrocytes and mixed hippocampal cultures | Deb and Gottschall, 1996 |
| MMP-9 | Yin Yang 1 | Binding to MMP-9 promoter to repress MMP-9 transcription | Rylski et al., 2008 |
| JunB | Repression of MMP-9 transcription in depolarized rat brain neuron | Rylski et al., 2009 | |
| Small molecule inhibitor of PAI-1 | Enhanced clearance of Aβ in brain by sustaining the plasmin proteolysis cascade | Jacobsen et al., 2008 | |
| Plasmin | PAI-1 (neuroserpin) | Inhibition of tissue plasminogen activator activity leading to reduced plasmin activity | Fabbro and Seeds, 2009 |
Aβ: Amyloid-β peptide, APLP: Amyloid precursor-like protein, APP: Amyloid precursor protein, HUCB-MSC: Human umbilical cord blood-derived mesenchymal stem cell, MMP: Matrix metalloproteinase, PAI-1: Plasminogen activator inhibitor-1, sICAM-1: Soluble in-tercellular adhesion molecule-1.