Bag5 Protects Neuronal Cells from Amyloid β-induced Cell Death

Abstract

The pathological mechanism of Alzheimer's disease (AD) needs to be elucidated. The Bcl-2 associated athanogene 5 (Bag5) is an important member in the Bag family. However, the role of Bag5 in AD has not yet been elucidated. In this study, we found that expression of Bag5 is elevated in the brains of AD transgenic Tg2576 mice at both mRNA levels and proteins. In vitro experiments indicated that Aβ1-42 treatment led to the upregulation of Bag5 in a dose-dependent manner. In addition, our results indicated that inhibition of Bag5 using small RNA interferences exacerbated Aβ1-42-induced neurotoxicity. On one hand, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assay demonstrated that inhibition of Bag5 exacerbated Aβ1-42-related cell death. On the other hand, silence of endogenous Bag5 promotes the generation of reactive oxygen species (ROS) and malondialdehyde (MDA) induced by Aβ1-42. Finally and importantly, it was shown that knockdown of Bag5 exacerbated Aβ1-42-induced apoptosis and caspase-3 cleavage. These data suggest that induction of Bag5 might have a neuroprotective effect in AD.

miR‑155 inhibition represents a potential valuable regulator in mitigating myocardial hypoxia/reoxygenation injury through targeting BAG5 and MAPK/JNK signaling

“…BAG5, as an important member of the BAG family, has been reported to demonstrate anti-apoptotic effects in prostate cancer (44). a previous study identified that BAG5 protected neuronal cells from amyloid β-induced cell death in Alzheimer's disease (45), and it has been demonstrated that BAG5 decreased the degradation of PTEN and maintained its stability through an ubiquitylation-dependent pathway (46). It has previously been observed that BAG5 may promote the accumulation of mutant p53 in tumors, and increase the gain-of-functions of mutant p53 (47).…”

miRNA‑770‑5p expression is upregulated in patients with type 2 diabetes and miRNA‑770‑5p knockdown protects pancreatic β‑cell function via targeting BAG5 expression

“…2A). As a member of the BAG protein family, which has been reported to enhance cell proliferation and survival (24), BAG5 is involved in several diseases via regulation of cell proliferation and gene expression (25)(26)(27)(28). Islet β-cell destruction and apoptosis serve an important role in the development of DM (29).…”

Stress-induced p53 drives BAG5 cochaperone expression to control α-synuclein aggregation in Parkinson's disease

“…BAG5, a member of the BAG family, is considered a pathogenic gene involved in dopaminergic neuronal degeneration [ 16 , 20 , 40 , 41 ]. It was reported that physiological stress increases BAG5 expression [ 18 , 42 , 43 ]. However, our screen reveals the uniqueness of the BAG5 cochaperone in stress-mediated responses in SH-SY5Y cells.…”