Indian Institute of Science (IISc) researchers have designed a small molecular fluorogenic probe that can sense a specific enzyme linked to the progression of Alzheimer’s disease. Such a probe can easily be fabricated into a strip-based kit that may enable on-site diagnosis.
Alzheimer’s disease, a neurodegenerative disorder, results in memory loss and compromises cognitive abilities in many people beyond the age of 60. Currently used techniques to detect manifestations of the disease (MRI, PET, and CT scans) are complex, expensive, and often produce inconclusive results, according to the researchers.
The molecular fluorogenic probe is designed by Debasis Das, assistant professor in the Department of Inorganic and Physical Chemistry at IISc., and Jagpreet Sidhu, a C.V. Raman postdoctoral fellow in the department.
“Our goal was to find a reliable, cost-effective solution. Fluorogenic probes are not fluorescent by themselves, but upon reaction with a target enzyme, they become fluorescent. Our target enzyme is Acetylcholinesterase (AChE),” said Mr Das.
Studies have shown that in the early stages of Alzheimer’s disease, AChE levels become imbalanced, thus making it a potential biomarker for the disease.
Brain cells, or neurons, secrete neurotransmitters — signalling molecules that instruct other cells to perform certain functions. Acetylcholine (ACh) is one such neurotransmitter. Its levels in our nervous system are tightly controlled by enzymes like AChE, which breaks it down into two parts — acetic acid and choline.
Current approaches determine AChE levels indirectly by measuring the levels of choline.
“They also often give confounding results because AChE has sister enzymes, such as butyrylcholinesterase and cholinesterase, that work on similar substrates, including ACh,” said Mr Das adding that they now have a proof-of-concept and a lead.
“Our goal is to take it to translation, in an Alzheimer’s disease model. For this, we need to modify the probe. Currently, the probe is UV-active, which can be harmful to tissues in high doses. These modifications would lead to the development of near-infrared active probes, which would be safer for living cells, and allow deep-tissue imaging. We are already quite close to doing this,” he added.
Apart from Alzheimer’s disease, such a probe can also be used for other applications, like detecting pesticide-related poisoning, as AChE can be inhibited by compounds used in some pesticides, Mr Sidhu said.
