Alzheimer’s disease (AD) belongs to the most common forms of dementia that causes a
progressive loss of brain cells and leads to memory impairment and decline of other thinking skills.
There is yet no effective treatment for AD; hence, the search for new drugs that could improve
memory and other cognitive functions is one of the hot research topics worldwide. Scientific efforts
are also directed toward combating behavioral and psychological symptoms of dementia, which are an
integral part of the disease. Several studies have indicated that glycogen synthase kinase 3 beta
(GSK3β) plays a crucial role in the pathogenesis of AD. Moreover, GSK3β inhibition provided
beneficial effects on memory improvement in multiple animal models of AD. The present review
aimed to update the most recent reports on the discovery of novel multifunctional ligands with GSK3β
inhibitory activity as potential drugs for the symptomatic and disease-modifying therapy of AD.
Compounds with GSK3β inhibitory activity seem to be an effective pharmacological approach for
treating the causes and symptoms of AD as they reduced neuroinflammation and pathological
hallmarks in animal models of AD and provided relief from cognitive and neuropsychiatric symptoms.
These compounds have the potential to be used as drugs for the treatment of AD, but their precise
pharmacological, pharmacokinetic, toxicological, and clinical profiles need to be defined.
Keywords: Alzheimer's disease, GSK3β, GSK3β inhibitors, memory impairment, multifunctional
ligands, neuroinflammation, procognitive activity.
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