Oxidative Stress Markers of Alzheimer's Disease in Peripheral Cell Mitochondria
Autor: | Asha Hewarathna, Ranu Pal, Elias K. Michaelis, Christian Schöneich, Lei Jiang |
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Rok vydání: | 2017 |
Předmět: |
Pathology
medicine.medical_specialty Cell Disease Biology Mitochondrion Pharmacology medicine.disease_cause Protein oxidation Biochemistry Peripheral Pathogenesis 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Physiology (medical) medicine 030212 general & internal medicine 030217 neurology & neurosurgery Oxidative stress Companion diagnostic |
Zdroj: | Free Radical Biology and Medicine. 108:S100 |
ISSN: | 0891-5849 |
DOI: | 10.1016/j.freeradbiomed.2017.04.321 |
Popis: | Alzheimer's disease (AD) represents a neurodegenerative disease leading to progressive dementia in the elderly. AD has been associated with increased oxidative stress and mitochondrial dysfunction. Hence, markers for oxidative stress are expected to accumulate not only in brain mitochondria, but also in mitochondria of peripheral cells. We have developed and optimized a method for the rapid and selective fluorogenic derivatization and enrichment of specific protein oxidation products, 3-nitrotyrosine and 3,4-dihydroxyphenylalanine (DOPA), in order to quantitatively compare protein oxidation in the mitochondria of peripheral, white blood cells obtained from healthy donors, patients with mild cognitive impairment (MCI), and AD patients. Double blind studies reveal a ca. two-fold increase of protein nitration/oxidation between mitochondrial proteins derived from healthy volunteers and MCI patients, with no further increase between MCI and AD patients. Proteomic studies will show whether specific proteins are target for nitration/oxidation during the pathogenesis of MCI and AD. Mitochondrial protein nitration/oxidation may be used for early screening of patients with the genetic risk for the development of AD or as companion diagnostic for pharmacological interventions. |
Databáze: | OpenAIRE |
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