Alzheimer’s disease (AD) characterized by a progressive neuronal loss and cognitive decline is the most prevalent form of neurodegenerative dementia. Currently, there is still no single confirmative clinically approved test to diagnose AD yet although one of the neuropathological hallmarks of AD, cerebral senile plaques can be visualized by positron emission tomography (PET). The plaques are mainly composed of amyloid-β (Aβ) peptides. It is known that deposition of Aβ appears a decade or more prior to the onset of any clinical symptoms of the disease. To achieve early detection and diagnostics of high-risk and pre-symptomatic subjects for AD, development of reliable diagnostic AD biomarkers and their detection tools/techniques are urgently needed for early intervention and treatment of the disease. The oxidative stress, overproduction of reactive oxygen species (ROS), is one of the prominent causes of neurotoxicity induced by Aβ, which is shown to eventually lead to neuronal cell death and then dementia. ROS is also shown to be an important therapeutic target in AD. Therefore, it is of great interest to develop a smart tool and/ technique that can directly detect and monitor the presence and the amount of Aβ-induced ROS in the high-risk and diseased brains as an alternative and reliable AD biomarker for disease diagnosis and evaluation of drug treatment efficacy. Toward this end, we propose herein the design and development of novel ratiometric two-photon fluorescent probes for sensing and monitoring of endogenous ROS in cell models of AD, living AD brain tissue and an AD mouse model in vivo. With such versatile probes, an investigation of the pathological effect of ROS, an evaluation of the disease progression for early diagnosis of AD and an assessment of drug treatment efficacy would then be achievable.
|Effective start/end date||1/09/21 → 31/08/24|
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