OCIAD1 contributes to neurodegeneration in Alzheimer's disease by inducing mitochondria dysfunction, neuronal vulnerability and synaptic damages
| العنوان: | OCIAD1 contributes to neurodegeneration in Alzheimer's disease by inducing mitochondria dysfunction, neuronal vulnerability and synaptic damages |
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| المؤلفون: | Xuping Li, Matthew D. Cykowski, Stephen T. C. Wong, Tiancheng He, Weiming Xia, Lin Wang, Joshua Chakranarayan, Suzanne Zein-Eldin Powell, Timothy Liu, Hong Zhao, Andreana L. Rivera |
| المصدر: | EBioMedicine EBioMedicine, Vol 51, Iss, Pp-(2020) |
| بيانات النشر: | Elsevier BV, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Candidate gene, Research paper, enOD1, endogenous OCIAD1, SFG, superior frontal gyrus, VDAC1, Voltage Dependent Anion Channel 1, lcsh:Medicine, β-tub, β-tubulin, Hippocampus, Disease, Mitochondrion, Mice, MMSE, Minimal Mental State Examination, 0302 clinical medicine, Hyperamyloidosis, OCIAD1, Olf, olfactory bulb, Membrane Potential, Mitochondrial, Neurons, lcsh:R5-920, Cell Death, Caspase 3, p53, tumor protein p53, SDHB, succinate dehydrogenase complex iron sulfur subunit B, Neurodegeneration, Brain, Cell Differentiation, General Medicine, Alzheimer's disease, Mitochondria, Up-Regulation, CTNNB1, β-catenin. CTX, cerebral cortex, HK1, hexokinase I. MCF, medial frontal cortex, Neoplasm Proteins, 3. Good health, Proto-Oncogene Proteins c-bcl-2, HIP, hippocampus, Veh, vehicle, DNT, dystrophic neurite, Mid, midbrain, 030220 oncology & carcinogenesis, HEK, human embryo kidney cell, lcsh:Medicine (General), VCX, primary visual cortex, VDAC1, Protein Binding, Mice, Transgenic, c-CAS9, Cleaved caspase-9, APP, amyloid precursor protein (A4), General Biochemistry, Genetics and Molecular Biology, Protein Aggregates, CER, cerebellum, 03 medical and health sciences, Alzheimer Disease, medicine, Animals, Humans, c-PARP, cleaved PARP, c-CAS3, cleaved caspase-3, mit-OD1, mitochondrial OCIAD1, MG, MG-132, exOD1, exogenous OCIAD1, OD1, OCIAD1, Amyloid beta-Peptides, Glycogen Synthase Kinase 3 beta, PUMA, p53 upregulated modulator of apoptosis, business.industry, F-Box Proteins, lcsh:R, MTL, mesial temporal lobe, EC, endorhinal cortex, medicine.disease, PCC, posterior cingulate cortex, Enzyme Activation, 030104 developmental biology, Superior frontal gyrus, Nerve Degeneration, Synapses, Commentary, SMAC, Second mitochondria-derived activator of caspase, Tumor Suppressor Protein p53, Mitochondrial dysfunction, business, Neuroscience |
| الوصف: | Background: Hyperamyloidosis in the brain is known as the earliest neuropathological change and a unique etiological factor in Alzheimer's disease (AD), while progressive neurodegeneration in certain vulnerable brain regions forms the basis of clinical syndromes. It is not clear how early hyperamyloidosis is implicated in progressive neurodegeneration and what factors contribute to the selective brain vulnerability in AD. Methods: Bioinformatics and experimental neurobiology methods were integrated to identify novel factors involved in the hyperamyloidosis-induced brain vulnerability in AD. We first examined neurodegeneration-specific gene signatures from sporadic AD patients and synaptic protein changes in young transgenic AD mice. Then, we systematically assessed the association of a top candidate gene with AD and investigated its mechanistic role in neurodegeneration. Findings: We identified the ovary-orientated protein OCIAD1 (Ovarian-Carcinoma-Immunoreactive-Antigen-Domain-Containing-1) as a neurodegeneration-associated factor for AD. Higher levels of OCIAD1, found in vulnerable brain areas and dystrophic neurites, were correlated with disease severity. Multiple early AD pathological events, particularly Aβ/GSK-3β signaling, elevate OCIAD1, which in turn interacts with BCL-2 to impair mitochondrial function and facilitates mitochondria-associated neuronal injury. Notably, elevated OCIAD1 by Aβ increases cell susceptibility to other AD pathological challenges. Interpretation: Our findings suggest that OCIAD1 contributes to neurodegeneration in AD by impairing mitochondria function, and subsequently leading to neuronal vulnerability, and synaptic damages. Funding: Ting Tsung & Wei Fong Chao Foundation, John S Dunn Research Foundation, Cure Alzheimer's Fund, and NIH R01AG057635 to STCW. Keywords: OCIAD1, Neurodegeneration, Hyperamyloidosis, Mitochondrial dysfunction, Alzheimer's disease |
| تدمد: | 2352-3964 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0bb861798d32c033f20fa2002b059bf7Test https://doi.org/10.1016/j.ebiom.2019.11.030Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0bb861798d32c033f20fa2002b059bf7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23523964 |
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