Year: 2019
Type: article
Abstract: Oxidative stress is a common feature of neurodegenerative diseases and plays an important role in disease progression. Appoptosin is a pro-apoptotic protein that contributes to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and progressive supranuclear palsy. However, whether appoptosin mediates oxidative stress-induced neurotoxicity has yet to be determined. Here, we observe that appoptosin protein levels are induced by hydrogen peroxide (H2O2) exposure through the inhibition of proteasomal appoptosin degradation. Furthermore, we demonstrate that overexpression of appoptosin induces apoptosis through the JNK-FoxO1 pathway. Importantly, knockdown of appoptosin can ameliorate H2O2-induced JNK activation and apoptosis in primary neurons. Thus, we propose that appoptosin functions as an upstream regulator of the JNK-FoxO1 pathway, contributing to cell death in response to oxidative stress during neurodegeneration.
Source: Frontiers in Aging Neuroscience
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
Funders: BrightFocus Foundation, Cure Alzheimer's Fund, National Natural Science Foundation of China, Natural Science Foundation of Fujian Province, Fujian Medical University, National Institutes of Health, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities, National Institute on Aging
Awards: G1614244694, G1851188853, G1981720942, G2273871270, G2568496843, G3080630271, Novel roles for the Alzheimer's Disease (AD) risk gene, SORLA in neuroprotection in AD, A role for TREM2/Abeta interactions in microglia-regulated AD pathogenesis, G838822281, G8627823389, Targeting Synaptic and Memory Deficits in Alzheimer's Disease
OpenAlex ID: W2969406449