Neural stem cell-conditioned medium upregulated the PCMT1 expression and inhibited the phosphorylation of MST1 in SH-SY5Y cells induced by Aβ25-35

Abstract

A progressive neurodegenerative disease, Alzheimer's disease (AD). Studies suggest that highly expressed protein isoaspartate methyltransferase 1 (PCMT1) in brain tissue. In the current study, we explored the effects of neural stem cell-conditioned medium (NSC-CDM) on the PCMT1/MST1 pathway to alleviate Aβ 25-35 -induced damage in SH-SY5Y cells. Our data suggested that Aβ 25-35 markedly inhibited cell viability. NSC-CDM or Neural stem cell-complete medium (NSC-CPM) had a suppression effect on toxicity when treatment with Aβ 25-35 , with a greater effect observed with NSC-CDM. Aβ 25-35 + NSC-CDM group exhibited an increase in PCMT1 expression. sh-PCMT1 markedly decreased cell proliferation and suppressed the protective role of NSC-CDM through the induction of apoptosis and improved p-MST1 expression. Overexpression of PCMT1 reversed the Aβ 25-35 -induced decrease in cell proliferation and apoptosis. In summary, our findings suggest that NSC-CDM corrects the Aβ 25-35induced damage to cells by improving PCMT1 expressions, which in turn reduces phosphorylation of MST1.

Whole-Genome Sequencing Analysis Reveals New Susceptibility Loci and Structural Variants Associated with Progressive Supranuclear Palsy

“…The odds ratio increased to 8.38 when comparing 1,244 individuals with homozygous deletions in PCMT1 with the rest of sample set. PCMT1 encodes a type [ class of protein carboxyl methyltransferase enzyme that is highly expressed in the brain 37 and is able to ameliorate Aβ 25-35 induced neuronal apoptosis 38,39 . Additionally, we found a deletion between CYP2F1 and CYP2A13 (chr19:41102802-41104285, AF = 0.17) and an insertion in SMCP (chr1:152880979-152880979, AF = 0.74) which were also significant ( Table 5 ).…”

“…The most significant signal is a 238 bp deletion in MAPT intron 9 (Fig. S10A, chr17:46009357-46009595, P = 3.14 × 10 -50 , AF = 0.16) that has been reported on the H2 haplotype [59,60] and is in LD (r 2 = 0.99) with the lead SNV, rs62057121 a type class of protein carboxyl methyltransferase enzyme that is highly expressed in the brain [61] and is able to ameliorate Aβ 25-35 induced neuronal apoptosis [62,63]. Additionally, we found a deletion between CYP2F1 and CYP2A13 (chr19:41102802-41104285, AF = 0.17) and an insertion in SMCP (chr1:152880979-152880979, AF = 0.74) which were also significant (Table 5).…”