Oxidative stress is a pathophysiological condition resulting in neurotoxicity, which is possibly associated with neurodegenerative disorders. In this study, the antioxidative effects of the antioxidant astaxanthin (AXT) in combination with huperzine A (HupA), which is used as a cholinesterase inhibitor for the treatment of Alzheimer's disease, were investigated. PC12 cells were treated with either tert‑butyl hydroperoxide (TBHP), or with the toxic version of β‑amyloid, Aβ25‑35, to induce oxidative stress and neurotoxicity. Cell viability, morphology, lactate dehydrogenase (LDH) release, intracellular accumulation of reactive oxygen species (ROS), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were determined, while neuroprotection was also monitored using an MTT assay. It was found that combining AXT with HupA significantly increased the viability of PC12 cells, prevented membrane damage (as measured by LDH release), attenuated intracellular ROS formation, increased SOD activity and decreased the level of MDA after TBHP exposure when compared to these drugs administered alone. Pretreatment with HupA and AXT decreased toxic damage produced by Aβ25‑35. These data indicated that combining an antioxidant with a cholinesterase inhibitor increases the degree of neuroprotection; with future investigation this could be a potential therapy used to decrease neurotoxicity in the brain.
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http://dx.doi.org/10.3892/mmr.2020.10920 | DOI Listing |
Neurochem Res
January 2025
Department of Physiology, Faculty of Medicine, University of Ondokuz Mayıs, Samsun, Türkiye.
In the present study, the effects of the acetylcholinesterase (AChE) enzyme inhibitor rivastigmine (RIVA) on spike-wave discharges (SWDs), memory impairment, anxiety-like behavior, and the transient receptor potential vanilloid 1 (TRPV1) gene expression were investigated in genetic absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. After tripolar electrodes were implanted on the WAG/Rij rats' skulls, single doses of 0.125, 0.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Amity Institute of Pharmacy, Amity University, Gurugram, Haryana, India.
Background: The current study aimed to investigate the chemical interaction of naringenin with the possible receptors and enzymes involved in the pathogenesis of cognitive deficits and tested their ADME and toxicity. Furthermore, in-vivo studies have also done to evaluate the effect of naringenin and its nanoparticles on STZ-induced cognitive decline in mice.
Method: Naringenin were evaluated against the active sites of β-secretase 1 (PDB: 3UQU), human insulin-degrading enzyme (PDB: 4RE9), insulin receptor tyrosine kinase (PDB: 1IR3), glycogen synthase kinase-3 β (PDB: 3L1S), phosphoprotein phosphatase 2A (PDB: 3P71), human superoxide dismutase I (PDB: 5YT0), catalase-3 (PDB:3EJ6), and human acetylcholinesterase (PDB: 4EY7) in comparison of rivastigmine using molecular docking studies.
Alzheimers Dement
December 2024
University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil.
Background: The increasing prevalence of neurodegenerative diseases, particularly among women post-menopause, is linked to the decline in 17 β estradiol (E2). Vitamin D deficiency, common in older individuals, exacerbates this risk due to its anti-inflammatory and neuroprotective properties. Hypovitaminosis D is associated with age-related conditions, including cognitive decline.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
UIPS, Panjab University, Chandigarh, Chandigarh, India.
Background: Sporadic Alzheimer's disease (sAD) is the most prevalent type of dementia, characterized by progressive neurodegeneration. Intracerebroventricular (ICV) administration of streptozotocin (STZ) serves as a model for sAD, inducing neurodegeneration through oxidative stress, apoptotic damage, mitochondrial dysfunction, and neuroinflammation. Fenchone, a monoterpenoid, has been reported to possess neuroprotective properties by attenuating oxidative stress, acetylcholinesterase activity, mitochondrial dysfunction and neuroinflammation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Nebraska Medical Center, Omaha, NE, USA.
Background: This pilot study addresses unmet needs for empirical evidence on real-world data (RWD) on sleep to inform pharmacological management in older adults at-risk for neurodegenerative conditions. Polypharmacy is prevalent among older adults, with potential adverse effects on physiological functions, including sleep. Sleep disturbances are prevalent in aging, may signal onset of Alzheimer's disease (AD), potentially contributing to the underlying pathology.
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