Estradiol exerts a neuroprotective effect on SH‐SY5Y cells through the miR‐106b‐5p/TXNIP axis

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease. Thioredoxin and thioredoxininteracting protein (TXNIP) complexes help sustain cell oxidation/reduction balance. In the present study, we verified the neuroprotective role of estradiol against amyloid-beta 42 in SH-SY5Y cells through inhibiting TXNIP expression, promoting cell viability and DNA synthesis ability, inhibiting cell apoptosis, and affecting caspase and Bax/Bcl-2 apoptotic signaling. miR-106b-5p could bind to TXNIP 3′-untranslated region to inhibit the expression level of TXNIP. Within SH-SY5Y cells, miR-106b-5p inhibition repressed cell viability and DNA synthesis ability and promoted cell apoptosis through caspase and Bax/ Bcl-2 apoptotic signaling, while miR-106b-5p overexpression or TXNIP knockdown exerted the opposite effects on SH-SY5Y cells; TXNIP knockdown remarkably attenuated the roles of miR-106b-5p inhibition. In conclusion, estradiol treatment on SH-SY5Y cells downregulates TXNIP expression and upregulates miR-106b-5p expression. miR-106b-5p exerts a neuroprotective effect on SH-SY5Y cells by promoting cell proliferation and inhibiting cell apoptosis through targeting TXNIP.

TXNIP: A Double-Edged Sword in Disease and Therapeutic Outlook

“…Bak reduces blood-brain barrier (BBB) damage, oxidative stress, and apoptosis by regulating TRX1/TXNIP expression and AMPK phosphorylation to weaken EBI after SAH [ 144 ]. Micro-RNAs like miR-17-5P [ 145 ], miR-106b-5p [ 146 ], and miR-20b [ 147 ], inhibits TXNIP expression, protecting brain cells. Thus, upregulation of mir-RNA appears to be a therapeutic target such as GW0742 [ 145 ] and estradiol [ 146 ], to protect brain cells from apoptosis and inflammation damage.…”

“…Micro-RNAs like miR-17-5P [ 145 ], miR-106b-5p [ 146 ], and miR-20b [ 147 ], inhibits TXNIP expression, protecting brain cells. Thus, upregulation of mir-RNA appears to be a therapeutic target such as GW0742 [ 145 ] and estradiol [ 146 ], to protect brain cells from apoptosis and inflammation damage. Dl-3-n-butylphthalide (Dl-NBP) treatment inhibits TXNIP-NLRP3 interaction and NLRP3 inflammasome activation by upregulating nuclear factor erythrocyte 2-related factor 2 (Nrf2) [ 148 ].…”

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

“…Overexpression of miRNA‐146a in SH‐SY5Y cells significantly decreased Lrp2 expression, resulting in an induction of proapoptotic Caspase‐3, thereby increasing cell apoptosis 42 . Table S1 summarizes the miRNAs in regulating cell apoptosis in multiple nerve cells mainly treated with Aβ 36–60 . ‘MiRNA‐mRNA’ axis is confirmed as a classic pattern in regulating cell apoptosis in multiple AD cellular models.…”

Influence of age and sex on microRNA response and recovery in the hippocampus following sepsis

“…On day 4, young and older males exhibited increased expression of miR-15a-5p, which may regulate estrogen signaling [83]. Indeed, for the 22 miRs that were increased on day 1 and day 4 in older males, several (miR-30b-5p, miR-342-3p, miR-30c-5p, miR-106b-5p, miR-672-5p) have been linked to estrogen responsiveness [84][85][86][87][88].…”