Oxalate-curcumin–based probe for micro- and macroimaging of reactive oxygen species in Alzheimer’s disease

Abstract

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.

Multiple reactivities of flavonoids towards pathological elements in Alzheimer's disease: structure–activity relationship

“…6 The prevailing perception of AD pathology reects the multifaceted quality of the disease. 2 Identication of additional pathological contributors of AD such as amyloid-b (Ab), 7 metal ions, 8 metal-bound Ab (metal-Ab), [9][10][11][12] and reactive oxygen species (ROS) 13 corroborates the complex nature of the disease. Ab, the major component of senile plaques, is an aggregation-prone peptide composed of 36-43 amino acid residues.…”

PL201, a Reported Rhamnoside Against Alzheimer's Disease Pathology, Alleviates Neuroinflammation and Stimulates Nrf2 Signaling

“…Since their structural complexity and multitarget activity, natural products and their derivatives are recognized as an important source for developing AD drug leads (28)(29)(30). For instance, curcumin and its derivatives have been reported to ameliorate multiple AD pathologies including inhibiting Aβ production and tau phosphorylation, reducing neuroinflammation and oxidative stress, promoting neural stem cell proliferation and adult neurogenesis, and reversing cognitive deficits (31)(32)(33). Rhamnoside is a common kind of naturally occurring glycoside with antiaging effects.…”

Design of a ratiometric two-photon probe for imaging of hypochlorous acid (HClO) in wounded tissues

“… 5 Mounting evidence has established a firm correlation between HClO and various biological and pathological activities ranging from inflammatory diseases to cancer, and immune and neurological diseases. 6 – 8 For these reasons, it is imperative to develop reliable methods to evaluate the fluctuation of HClO levels in cells and tissues.…”