Title:Recent Advances in the Discovery of GSK-3 Inhibitors from Synthetic Origin in the Treatment of Neurological Disorders
Volume: 22
Issue: 12
关键词:
GSK-3，受体，阿尔茨海默，帕金森，Tau蛋白，神经保护，抑郁。
摘要:
Background: Glycogen synthase kinase 3 (GSK-3) is a serine/threonine kinase enzyme
that controls neuronal functions such as neurite outgrowth, synapse formation, neurotransmission,
and neurogenesis. The enzyme has two subunits as GSK-3α and GSK-3β. 4ACC, 1Q3D, 3AFG,
1UV5, and 1Q5K are the important GSK-3 receptors isolated from Homo sapiens and Mus musculus.
This enzyme mainly phosphorylates Tau protein with the increased amount in neuronal fibres
together with beta-amyloid plaques that cause neuronal diseases like Alzheimer's, Parkinson’s and
many more.
Objective: We investigated the developments of various synthetic GSK-3 inhibitors responsible for
the prevention and treatment of neurological disorders, like Alzheimer's disease, bipolar disorders,
acting as antidepressants, neuroprotective, etc.
Results and Conclusion: It has been observed that structures of the GSK-3 inhibitors are comprised
of benzopyridine, benzothiazole, pyrazole, pyrazine, dioxolo-benzoxazine, oxadiazole, and
benzimidazole in the skeletal with cyclopropyl amide, phenyl carbamothioate, 3-[(propan-
2-yl)oxy]propan-1-amine in the side chain. The molecules were evaluated against the effectivity
of GSK-3, human adenosine kinase, cyclin-dependent kinase, and phosphodiesterase-4 along
with tail suspension test forced swim test, percent neuronal survival and other cognitive behaviours.
The observations confirmed the remarkable effects of the synthesized molecules to conquer
Alzheimer, Parkinson’s depression, psychosis and other forms of neurological disorders.
