Year: 2012
Type: article
Abstract: Apoptosis is an essential cellular process in multiple diseases and a major pathway for neuronal death in neurodegeneration. The detailed signaling events/pathways leading to apoptosis, especially in neurons, require further elucidation. Here we identify a β-amyloid precursor protein (APP)-interacting protein, designated as appoptosin, whose levels are upregulated in brain samples from Alzheimer's disease and infarct patients, and in rodent stroke models, as well as in neurons treated with β-amyloid (Aβ) and glutamate. We further demonstrate that appoptosin induces reactive oxygen species release and intrinsic caspase-dependent apoptosis. The physiological function of appoptosin is to transport/exchange glycine/5-amino-levulinic acid across the mitochondrial membrane for heme synthesis. Downregulation of appoptosin prevents cell death and caspase activation caused by glutamate or Aβ insults. APP modulates appoptosin-mediated apoptosis through interaction with appoptosin. Our study identifies appoptosin as a crucial player in apoptosis and a novel pro-apoptotic protein involved in neuronal cell death, providing a possible new therapeutic target for neurodegenerative disorders.
Source: Journal of Neuroscience
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funders: Alzheimer's Association, American Health Assistance Foundation, National Natural Science Foundation of China, Natural Science Foundation of Fujian Province, Fok Ying Tung Education Foundation, National Institutes of Health, Program for New Century Excellent Talents in University, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities, National Institute on Aging, National Institute of Neurological Disorders and Stroke
Awards: ApoE Receptor Biology and Neurodegeneration, The Role of Appoptosin in Alzheimer's Disease and Other Tauopathies, ApoE pathway in cerebrovascular Aβ clearance in Alzheimer's disease, Transcriptional Regulation of BACE and the Components of the gamma-Secretase Comp, Regulation of Protein Trafficking in Neurodegeneration, a-synuclein clearance strategies for the treatment of Lewy body disease, a-Synuclein vulnerability mechanisms and therapeutics in Alzheimer's Disease, Dapper蛋白在小鼠胚胎发育和器官形成中的作用及其机制, Generation of a Transgenic Mouse Model for Functional Study of a Novel Gene FG01, UCSD Alzheimer's Disease Research Center P50, G3457996028, PTEN, Cell Cycle and Neurofibrillary Degeneration, CutA interacts with BACE1 and participates in Alzheimer's disease, G486772123, Identifying and characterizing gene(s) involved in beta-amyloid production., New Roles for sAPP in Neuroprotection and Neurogenesis, G849861852, ApoE and LRP1 in brain insulin signaling and glucose metabolism (Competitive Renewal), Regional, Synaptic, Cellular Modulation of Abeta Metabolism
OpenAlex ID: W2033166503