Altered expression of insulin‐degrading enzyme and regulator of calcineurin in the rat intracerebral streptozotocin model and human apolipoprotein E‐ε4–associated Alzheimer's disease
| Autor: | Ming Tong, Natalia Moriel, Büşra Delikkaya, Gina Gallucci, Suzanne M. de la Monte |
|---|---|
| Přispěvatelé: | İÜC, Cerrahpaşa Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü |
| Rok vydání: | 2019 |
| Předmět: |
Apolipoprotein E
medicine.medical_specialty lcsh:Geriatrics lcsh:RC346-429 03 medical and health sciences 0302 clinical medicine Insulin resistance Internal medicine mental disorders Genetics Insulin-degrading enzyme Medicine Insulin‐degrading enzyme Neurodegeneration lcsh:Neurology. Diseases of the nervous system 030304 developmental biology 0303 health sciences Messenger RNA biology Streptozotocin business.industry Alzheimer's disease medicine.disease Calcineurin lcsh:RC952-954.6 Psychiatry and Mental health Insulin receptor Endocrinology biology.protein Neurology (clinical) RCAN1 business 030217 neurology & neurosurgery Insulin deficiency medicine.drug |
| Zdroj: | Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, Vol 11, Iss 1, Pp 392-404 (2019) Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring |
| ISSN: | 2352-8729 |
| DOI: | 10.1016/j.dadm.2019.03.004 |
| Popis: | Introduction: This study assesses insulin-degrading enzyme (IDE) and regulator of calcineurin 1 (RCAN1) as potential mediators of brain insulin deficiency and neurodegeneration in experimental and human Alzheimer's disease (AD). Methods: Temporal lobes from Long Evans rats treated with intracerebral streptozotocin or vehicle and postmortem frontal lobes from humans with normal aging AD (Braak 0-2), moderate (Braak 3-4) AD, or advanced (Braak 5-6) AD were used to measure IDE and RCAN mRNA and protein. Results: Intracerebral streptozotocin significantly increased IDE and RCAN mRNA and protein. In humans with apolipoprotein E (ApoE) ε3/ε4 or ε4/ε4 and AD, IDE was elevated at Braak 3-4, but at Braak 5-6, IDE expression was significantly reduced. RCAN1 mRNA was similarly reduced in ApoE ε4+ patients with moderate or severe AD, whereas RCAN1 protein declined with the severity of AD and ApoE ε4 dose. Discussion: The findings suggest that IDE and RCAN1 differentially modulate brain insulin signaling in relation to AD severity and ApoE genotype. © 2019 National Institutes of Health The authors thank Dr Emine B. Yalcin for assisting with technical aspects of the qRT-PCR studies. This research was supported by grants AA11431, AA024092, and NS096525 from the National Institutes of Health. |
| Databáze: | OpenAIRE |
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