Apolipoprotein E ablation decreases synaptic vesicular zinc in the brain
| Autor: | Ashley I. Bush, Richard D. Palmiter, Dong-Kyu Kim, Eunsil Cho, Jae-Young Koh, Irene Volitakis, Joo Yong Lee, Tae-Youn Kim, Jong S. Kim |
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| Rok vydání: | 2010 |
| Předmět: |
Apolipoprotein E
medicine.medical_specialty Adaptor Protein Complex 3 Iron chemistry.chemical_element Zinc Neuropathology Synaptic vesicle General Biochemistry Genetics and Molecular Biology Apolipoproteins E Biomaterials Amyloid beta-Protein Precursor Mice Alzheimer Disease Internal medicine medicine Animals Cation Transport Proteins Mice Knockout Metals and Alloys Brain Membrane Proteins Membrane Transport Proteins medicine.disease Protein Subunits Endocrinology chemistry Biochemistry Knockout mouse lipids (amino acids peptides and proteins) Cerebral amyloid angiopathy Synaptic Vesicles Alzheimer's disease General Agricultural and Biological Sciences Carrier Proteins Copper |
| Zdroj: | Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. 23(6) |
| ISSN: | 1572-8773 |
| Popis: | Both apolipoprotein E (apoE) and zinc are involved in amyloid β (Aβ) aggregation and deposition, in the hallmark neuropathology of Alzheimer’s disease (AD). Recent studies have suggested that interaction of apoE with metal ions may accelerate amyloidogenesis in the brain. Here we examined the impact of apoE deficiency on the histochemically reactive zinc pool in the brains of apoE knockout mice. While there was no change in total contents of metals (zinc, copper, and iron), the level of histochemically reactive zinc (principally synaptic zinc) was significantly reduced in the apoE-deficient brain compared to wild-type. This reduction was accompanied by reduced expressions of the presynaptic zinc transporter, ZnT3, as well as of the δ-subunit of the adaptor protein complex-3 (AP3δ), which is responsible for post-translational stability and activity of ZnT3. In addition, the level of histochemically reactive zinc was also decreased in the cerebrovascular micro-vessels of apoE-deficient mice, the site of cerebral amyloid angiopathy in AD. These results suggest that apoE may affect the cerebral free zinc pool that contributes to AD pathology. |
| Databáze: | OpenAIRE |
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