HKBU develops versatile compound F-SLOH for Alzheimer’s disease treatment

Description

HKBU scientists develop versatile compound for Alzheimer’s disease treatment

 

A study led by researchers from Hong Kong Baptist University (HKBU) has demonstrated that a multifunctional organic compound named F-SLOH has the potential to treat Alzheimer’s disease (AD) in early stage by inhibiting the accumulation of amyloid-beta (Aβ) and tau proteins, the pathological hallmarks of AD, in brains. The findings have been published in the international scientific journal Redox Biology.

 

AD is the most common cause of dementia. It accounts for nearly 65% of dementia in Hong Kong Chinese elderly. It is pathologically characterised by the abnormal accumulation of Aβ and tau proteins in brains, which cause progressive neuronal loss and cognitive impairments. Currently there is no cure for AD, and the available medicines can only relieve its symptoms. Inhibiting the formation of Aβ is considered the primary and a promising therapeutic approach to treat AD.

 

F-SLOH as theranostic agent for AD

 

In the search for novel therapeutic and diagnostic methods for AD, a research team comprising Professor Li Min, Professor of the Teaching and Research Division and Associate Dean of the School of Chinese Medicine; Professor Ricky Wong Man-shing, Professor of the Department of Chemistry; and Dr Iyaswamy Ashok, Research Assistant Professor of the Teaching and Research Division of the School of Chinese Medicine at HKBU demonstrated the in vivo therapeutic efficacy of a compound called F-SLOH in reducing the levels of Aβ and Tau proteins, and improving the learning and memory functions of mice with AD. The team also unveiled the mechanism of how F-SLOH induces the neuropathological changes.

 

F-SLOH is a multi-functional cyanine probe synthesised by HKBU chemical scientists for the detection of biological materials such as protein and peptides. Its features include real-time visualisation of Aβ in brains, excellent permeability to the brain and low bio-toxicity. Previous studies showed that F-SLOH could inhibit Aβ species and their aggregation as well as provide neuroprotection against Aβ-induced toxicity in vitro at the cellular level.

 

F-SLOH

 

To determine the therapeutic efficacy of F-SLOH for AD, the researchers injected or fed F-SLOH to a group of transgenic AD mice for months. Histopathology and biochemical analyses showed that in mice treated with F-SLOH, Aβ oligomers (one of the Aβ species), Aβ plaque deposits (the clumps of Aβ) were dramatically reducedin their hippocampus as well as the entire brain compared to the AD mice in the control group without F-SLOH application.

 

The researchers also found that F-SLOH can reduce the amyloid precursor protein that generates Aβ, and reduce the level of tau protein. In an immunoblotting analysis of the brain of the transgenic AD mice, the F-SLOH treatment group showed significant reduction of the amyloid precursor protein and its metabolites compared to the control group.