Title:Casein Kinase 1δ Inhibitors as Promising Therapeutic Agents for
Neurodegenerative Disorders
Volume: 29
Issue: 27
关键词:
酪蛋白激酶1δ,酪蛋白激酶1δ抑制剂,神经保护剂,抗癌剂,小分子,天然抑制剂,药物设计。
摘要: Casein kinase 1 (CK1) belongs to the serine-threonine kinase family and is expressed
in all eukaryotic organisms. At least six human isoforms of CK1 (termed α, γ1-3,
δ and ε) have been cloned and characterized. CK1δ isoform modulates several physiological
processes, including DNA damage repair, circadian rhythm, cellular proliferation and
apoptosis. Therefore, CK1δ dysfunction may trigger diverse pathologies, such as cancer,
inflammation and central nervous system disorders. Overexpression and aberrant activity
of CK1δ have been connected to hyperphosphorylation of key proteins implicated in the
development of neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases
and Amyotrophic Lateral Sclerosis. Thus, CK1δ inhibitors have attracted attention
as potential drugs for these pathologies and several compounds have been synthesized or
isolated from natural sources to be evaluated for their CK1δ inhibitory activity. Here we
report a comprehensive review on the development of CK1δ inhibitors, with a particular
emphasis on structure-activity relationships and computational studies, which provide
useful insight for the design of novel inhibitors.