OCIAD1 contributes to neurodegeneration in Alzheimer's disease by inducing mitochondria dysfunction, neuronal vulnerability and synaptic damages
| Autor: | 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 |
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| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | EBioMedicine EBioMedicine, Vol 51, Iss, Pp-(2020) |
| ISSN: | 2352-3964 |
| DOI: | 10.1016/j.ebiom.2019.11.030 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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