Superoxide-responsive fluorogenic molecular probes for optical bioimaging of neurodegenerative events in Alzheimer’s disease

The Analyst ◽  
2021 ◽  
Author(s):  
Jawon Shin ◽  
Dong Min Kang ◽  
Jounghyun Yoo ◽  
Jeongyun Heo ◽  
Keunsoo Jeong ◽  
...  

Since oxidative stress has been recognized as a major factor contributing to the progression of several neurodegenerative disorder, reactive oxygen species (ROS) including superoxide have received great attention as a...

Author(s):  
Marta Goschorska ◽  
Izabela Gutowska ◽  
Irena Baranowska-Bosiacka ◽  
Katarzyna Piotrowska ◽  
Emilia Metryka ◽  
...  

It has been reported that donepezil and rivastigmine, the acetylcholinesterase (AchE) inhibitors commonly used in the treatment of Alzheimer’s disease (AD), do not only inhibit AChE but also have antioxidant properties. As oxidative stress is involved in AD pathogenesis, in our study we attempted to examine the influence of donepezil and rivastigmine on the activity of antioxidant enzymes and glutathione concentration in macrophages—an important source of reactive oxygen species and crucial for oxidative stress progression. The macrophages were exposed to sodium fluoride induced oxidative stress. The antioxidant enzymes activity and concentration of glutathione were measured spectrophotometrically. The generation of reactive oxygen species was visualized by confocal microscopy. The results of our study showed that donepezil and rivastigmine had a stimulating effect on catalase activity. However, when exposed to fluoride-induced oxidative stress, the drugs reduced the activity of some antioxidant enzymes (Cat, SOD, GR). These observations suggest that the fluoride-induced oxidative stress may suppress the antioxidant action of AChE inhibitors. Our results may have significance in the clinical practice of treatment of AD and other dementia diseases.


2018 ◽  
Vol 7 (10) ◽  
pp. 329 ◽  
Author(s):  
Yu-Te Lin ◽  
Yi-Chung Wu ◽  
Gwo-Ching Sun ◽  
Chiu-Yi Ho ◽  
Tzyy-Yue Wong ◽  
...  

Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer’s disease (AD). However, the relationships among AD, hypertension, and oxidative stress remain to be elucidated. Here, we aimed to determine whether reactive oxygen species (ROS) reduction by resveratrol in the brain leads to cognitive impairment reduction in rats with angiotensin II (Ang-II)-induced early AD. Male Wistar Kyoto (WKY) rats with Ang-II-induced AD were treated with losartan or resveratrol for two weeks. Our results show decreased blood pressure, increased hippocampal brain-derived neurotrophic factor (BDNF) level, and decreased nucleus tractus solitarius (NTS) ROS production in the Ang-II groups with losartan (10 mg/kg), or resveratrol (10 mg/kg/day) treatment. Furthermore, losartan inhibition of hippocampal TauT231 phosphorylation activated AktS473 phosphorylation, and significantly abolished Ang-II-induced Aβ precursors, active caspase 3, and glycogen synthase kinase 3β (GSK-3β)Y216 expressions. Consistently, resveratrol showed similar effects compared to losartan. Both losartan and resveratrol restored hippocampal-dependent contextual memory by NADPH oxidase 2 (NOX2) deletion and superoxide dismutase 2 (SOD2) elevation. Our results suggest that both losartan and resveratrol exert neuroprotective effects against memory impairment and hippocampal damage by oxidative stress reduction in early stage AD rat model. These novel findings indicate that resveratrol may represent a pharmacological option similar to losartan for patients with hypertension at risk of AD during old age.


2015 ◽  
Vol 61 (1) ◽  
pp. 57-69 ◽  
Author(s):  
E.E. Dubinina ◽  
L.V. Schedrina ◽  
N.G. Neznanov ◽  
N.M. Zalutskaya ◽  
D.V. Zakharchenko

The paper summarizes literature data on the importance of oxidative stress as one of the pathogenetic mechanisms in Alzheimer's disease. The paper describes the main specific and nonspecific ways of reactive oxygen species generation in the course of the disease development. The effect of reactive oxygen species generated by the functional activity of cells, i.e. apoptosis and mitotic cycle, is shown. The role of the regulatory system of nodal cells is performed by phosphorylation/dephosphorylation process which is associated with intense phosphorylation of tau protein and mitosis-specific proteins. In Alzheimer's disease, the regulating function of peptidyl-prolyl isomerases in particular of Pin1 associated with maintaining a balanced state of phosphorylation/dephosphorylation processes is disturbed. Taking into consideration the multifactorial impairment of the cell cycle control, this process should be considered from the standpoint of the general state of metabolic processes, and oxidative stress has one of the key positions in aging.


2002 ◽  
Vol 82 (2) ◽  
pp. 305-315 ◽  
Author(s):  
Seigo Tanaka ◽  
Masanori Takehashi ◽  
Naomi Matoh ◽  
Shinya Iida ◽  
Tomoki Suzuki ◽  
...  

2017 ◽  
Vol 114 (47) ◽  
pp. 12384-12389 ◽  
Author(s):  
Jian Yang ◽  
Xueli Zhang ◽  
Peng Yuan ◽  
Jing Yang ◽  
Yungen Xu ◽  
...  

Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder that has a progression that is closely associated with oxidative stress. It has long been speculated that the reactive oxygen species (ROS) level in AD brains is much higher than that in healthy brains. However, evidence from living beings is scarce. Inspired by the “chemistry of glow stick,” we designed a near-IR fluorescence (NIRF) imaging probe, termed CRANAD-61, for sensing ROS to provide evidence at micro- and macrolevels. In CRANAD-61, an oxalate moiety was utilized to react with ROS and to consequentially produce wavelength shifting. Our in vitro data showed that CRANAD-61 was highly sensitive and rapidly responsive to various ROS. On reacting with ROS, its excitation and emission wavelengths significantly shifted to short wavelengths, and this shifting could be harnessed for dual-color two-photon imaging and transformative NIRF imaging. In this report, we showed that CRANAD-61 could be used to identify “active” amyloid beta (Aβ) plaques and cerebral amyloid angiopathy (CAA) surrounded by high ROS levels with two-photon imaging (microlevel) and to provide relative total ROS concentrations in AD brains via whole-brain NIRF imaging (macrolevel). Lastly, we showed that age-related increases in ROS levels in AD brains could be monitored with our NIRF imaging method. We believe that our imaging with CRANAD-61 could provide evidence of ROS at micro- and macrolevels and could be used for monitoring ROS changes under various AD pathological conditions and during drug treatment.


Sign in / Sign up

Export Citation Format

Share Document