Exploring Whether Iron Sequestration within the CNS of Patients with Alzheimer’s Disease Causes a Functional Iron Deficiency That Advances Neurodegeneration
Abstract
The involvement of iron in the pathogenesis of Alzheimer’s disease (AD) may be multifaceted. Besides potentially inducing oxidative damage, the bioavailability of iron may be limited
within the central nervous system, creating a functionally iron-deficient state. By comparing staining
results from baseline and modified iron histochemical protocols, iron was found to be more tightly
bound within cortical sections from patients with high levels of AD pathology compared to subjects
with a diagnosis of something other than AD. To begin examining whether the bound iron could cause
a functional iron deficiency, a protein-coding gene expression dataset of initial, middle, and advanced
stages of AD from olfactory bulb tissue was analyzed for iron-related processes with an emphasis
on anemia-related changes in initial AD to capture early pathogenic events. Indeed, anemia-related
processes had statistically significant alterations, and the significance of these changes exceeded
those for AD-related processes. Other changes in patients with initial AD included the expressions
of transcripts with iron-responsive elements and for genes encoding proteins for iron transport and
mitochondrial-related processes. In the latter category, there was a decreased expression for the
gene encoding pitrilysin metallopeptidase 1 (PITRM1). Other studies have shown that PITRM1 has
an altered activity in patients with AD and is associated with pathological changes in this disease.
Analysis of a gene expression dataset from PITRM1-deficient or sufficient organoids also revealed
statistically significant changes in anemia-like processes. These findings, together with supporting
evidence from the literature, raise the possibility that a pathogenic mechanism of AD could be a
functional deficiency of iron contributing to neurodegeneration.
About the Authors
List of references
Таджиев Б. М. и др. КЛИНИЧЕСКИЕ ПРОЯВЛЕНИЯ ГЕРПЕТИЧЕСКОЙ ИНФЕКЦИИ У ВИЧ ИНФИЦИРОВАННЫХ ДЕТЕЙ //International Scientific and Practical Conference World science. – ROST, 2018. – Т. 4. – №. 4. – С. 42-44.
Daminova X. M. Modern view to optimization of the diagnosis of the course of parkinson’s disease //New Day in Medicine. – 2022. – Т. 1. – С. 39.
Маличенко С. Б., Колесова И. Р. Изучение клинической эффективности и переносимости препарата Терафлекс (глюкозамин гидрохлорид-500 мг и натрий хондроитин сульфата-400 мг) при суставном синдроме у женщин в физиологической и хирургической менопаузе (отчет) //Отчет. М. – 2005.
Асадуллаев М. М., Расулова Х. А., Даминова Х. М. Значение нейроактивных аминокислот и окиси азота в патогенезе острых мозговых инсультов //Журн. неврол. и психиатр. им. СС Корсакова. Приложение «Инсульт. – 2003. – №. 9. – С. 143.
Даминова Х. М. и др. Тактика лечения и восстановительных мероприятий у больных с ишемическим инсультом //Новый день в медицине. – 2019. – №. 2. – С. 22-24.
Tadzhiev B. M. et al. Clinical manifestations of herpetic infection in HIV-infected children //World Science. – 2018. – Т. 4. – №. 4. – С. 42-4.
Даминова Х. М. Нейропротекция; несоответствие между данными получаемые эксперементальными и клиническими исследованиями //Журнал неврология. – 2016. – №. 3-С. – С. 61.
Даминова М. Н. и др. Особенности течения гименолепидоза у детей с оценкой лечения //Новый день в медицине. – 2020. – №. 2. – С. 347-349.
Shohimardonov S. H., Daminova K. Examining level of hemoglobin in patients with parkinson's disease and the role of hemoglobin level in the disease course //MOVEMENT DISORDERS. – 111 RIVER ST, HOBOKEN 07030-5774, NJ USA : WILEY, 2019. – Т. 34.
Даминова Х. М., Саидвалиев Ф. С. РОЛЬ БИОМАРКЕРОВ ПРОДРОМАЛЬНОЙ СТАДИИ БОЛЕЗНИ ПАРКИНСОНА В ПРОГРЕССИРОВАНИИ ЗАБОЛЕВАНИЯ //ЖУРНАЛ НЕВРОЛОГИИ И НЕЙРОХИРУРГИЧЕСКИХ ИССЛЕДОВАНИЙ. – 2022. – Т. 3. – №. 2.
Кодиров А. Э. и др. РОЛЬ ПОЛИМОРФНЫХ ВАРИАНТОВ ГЕНОВ IL17A И ЦИТОХРОМА P450 ПРИ БОЛЕЗНИ ГРЕЙВСА //Биология. – 2022. – №. 5. – С. 139.
Khadjibaev F. et al. The first successful kidney transplant to a child with abnormality of urinary tract in Uzbekistan: case report //Experimental and Clinical Transplantation. – 2020. – Т. 18. – №. 1. – С. 44-46.
Ruzibakieva M. et al. Interleukin-1 gene polymorphisms role in development of chronic glomerulonephritis and ESRD //European Journal of pharmaceutical and medical research. – 2019. – Т. 6. – №. 6. – С. 300-303.
Kamalov Z. S. et al. Helicobacter pylori and host gene polymorphism of tnf rs1800629 in patients with gastroduodenal pathology //J Cardiovasc. Dis. Res. – 2021. – Т. 12. – №. 3. – С. 272-276.
Ruzibakieva M. R. et al. Gender differences in the distribution of HLA II markers in chronic glomerulonephritis and chronic kidney disease in Uzbek population //European science review. – 2017. – №. 1-2. – С. 110-113.
Kamalov Z. S. et al. SIGNIFICANCE OF CYTOKINE GENES IN HBV INFECTION //E Conference Zone. – 2023. – С. 48-49.
Raufov A. A., Ya F. N., Ruzibakieva M. R. Frequency Of Cyp3a5 (A6986g) Gene Polymorphism In Patients With BA, COPD, And ACO //Procedia of Social Sciences and Humanities. – 2022. – Т. 2. – С. 44-46.
Khadjibaev A. et al. Three-Year Experience of Kidney Transplantation at a Single Center in Uzbekistan //Experimental and Clinical Transplantation. – 2022. – Т. 1. – С. 24-30.
Ruzibakieva M. et al. The meaning of two loci HLA class II haplotypes distribution in chronic glomerulonephritis and chronic kidney disease in uzbek population //European journal of pharmaceutical and medical research. – 2018. – Т. 5. – №. 6. – С. 420-23.
Закирова Л. Т., Нишанов Д. А., Алимходжаева Л. Т. Прогностическая значимость иммуногистохимических маркеров RE, RP, HER2/neu рака молочной железы у женщин молодого возраста //Евразийский онкологический журнал. – 2015. – №. 3. – С. 42-47.
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