GSK-3 - Disease Relevance

Disease Relevance

Due to its involvement in a great number of signaling pathways, GSK-3 has been associated with a host of high-profile diseases. GSK-3 inhibitors are currently being tested for therapeutic effects in Alzheimer’s disease, Type II diabetes (Diabetes mellitus type 2), some forms of cancer, and Bipolar Disorder

It has now been shown that Lithium, which has been used as a treatment for bi-polar disorder, acts as a mood stabilizer by selectively inhibiting GSK-3. The mechanism through which GSK-3 inhibition stabilizes mood is not known, though it is suspected that the inhibition of GSK-3’s ability to promote inflammation contributes to the therapeutic effect.

GSK-3 activity has been associated with both pathological features of Alzheimer’s disease, namely the buildup of Amyloid-β (Aβ) deposits and the formation of neurofibrillary tangles. GSK-3 is thought to directly promote Aβ production and to be tied to the process of the hyperphosphorylation of tau proteins, which leads to the tangles. Due to these roles of GSK-3 in promoting Alzheimer’s disease, GSK-3 inhibitors may have positive therapeutic effects on Alzheimer’s patients and are currently in the early stages of testing.

In a similar fashion, targeted inhibition of GSK-3 may have therapeutic effects on certain kinds of cancer. Though GSK-3 has been shown to promote apoptosis in some cases, it has also been reported to be a key factor in tumorigenesis in some cancers. Supporting this claim, GSK-3 inhibitors have been shown to induce apoptosis in glioma and pancreatic cancer cells.

GSK-3 inhibitors have also shown promise in the treatment of type-II diabetes. Though GSK-3 activity under diabetic conditions can differ radically across different tissue types, studies have shown that introducing competitive inhibitors of GSK-3 can increase glucose tolerance in diabetic mice. The role that inhibition of GSK-3 might play across its other signaling roles is not yet entirely understood.