miR-590-5p Overexpression Alleviates β-Amyloid-Induced Neuron Damage via Targeting Pellino-1

Abstract

Alzheimer’s disease (AD) is one common degenerative disorder. However, the effects of miR-590-5p on AD and the mechanism on modulation of AD development were unclear. In this study, the miR-590-5p level in AD patients at mild, moderate, and severe stage as well as APP/PS1 transgenic mice was detected by qRT-PCR. The relationship of miR-590-5p and pellino-1 (PELI1) was identified by double luciferase reporter gene assay. Afterwards, both BV-2 and HT22 cells were exposed to β-amyloid (Aβ) peptides to mimic AD cell model. Then, the roles of miR-590-5p upregulation or PELI1 silence in cell proliferation and apoptosis were explored by CCK-8 assay and TUNEL assay, and the expression of apoptosis-related proteins was detected by western blotting. Furthermore, the involvements of the downstream Traf3/MAPK P38 pathway with the roles of miR-590-5p in AD were measured by western blotting. Our results showed that knockdown of miR-590-5p was found in AD patients, mice model, and Aβ-induced cell model. Notably, PELI1 was proved as a target gene of miR-590-5p. miR-590-5p mimic or PELI1 silence significantly promoted cell proliferation and inhibited cell apoptosis, as well as suppressed the activation of Traf3/MAPK P38 pathway both in Aβ-induced BV-2 and HT22 cells. The effects of PELI1 overexpression on cell proliferation, apoptosis, and Traf3/MAPK P38 pathway were partly abrogated by miR-590-5p mimic both in BV-2 and HT22 cells. In conclusion, miR-590-5p was expressed at lower levels in AD, and miR-590-5p/PELI1 axis might be involved in the progression of AD by the downstream Traf3/MAPK P38 pathway.

MicroRNAs and MAPKs: Evidence of These Molecular Interactions in Alzheimer’s Disease

“…According to the findings, the anti-apoptotic effect of miRNA might partly be due to the inhibition of Pellino-1 (PELI1), which increased TRAF3 but decreased the expression as well as the phosphorylation of p38 MAPK and ERK1/2. Consistently, activation of the p38 MAPK pathway has been previously found in the brain tissue of AD cases [184].…”

“…Using both BV-2 and HT22 cells stimulated with Aβ as an in vitro AD model, Shang et al [184] found that miR-590-5p mimic injection restored cell viability by improving proliferation. In addition, miR-590-5p levels were found to be reduced in the serum of both AD patients and APP/PS1 transgenic mice.…”

Epigenetic Regulation of Neuroinflammation in Alzheimer’s Disease

“…In addition, the E3 ligase Pellino, expressed in a variety of nerve cells, is a key regulator of microglia-mediated autoimmune neuroinflammation, and it is engaged in the ubiquitination and degradation process of c/EBPβ. The depletion of Pelil can increase the expression of c/EBPβ and CD36, thereby promoting the phagocytic activity of microglia to further improve the clearance of Aβ [ 135 , 136 ]. Pleckstrin homology-like domain family A member 1 (PHLDA1) is an important modulator of microglia-mediated inflammation.…”

NcRNAs: A synergistically antiapoptosis therapeutic tool in Alzheimer's disease

“…MiR‐485‐3p‐CD36 axis weakened the phagocytosis of Aβ in vitro and in vivo and might promote cell apoptosis in AD 138 . Table S3 summarizes all the abnormally expressed and cell apoptosis‐related miRNAs in AD patients 132–160 . These miRNAs can form ‘miRNA‐mRNA’ axis in regulating cell apoptosis in AD.…”

“… 138 Table S3 summarizes all the abnormally expressed and cell apoptosis‐related miRNAs in AD patients. 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 These miRNAs can form ‘miRNA‐mRNA’ axis in regulating cell apoptosis in AD.…”