Lithium has been used to treat bipolar disorder for nearly half a century now, even though lithium’s therapeutic mechanism has remained an enigma. No one is absolutely sure how lithium is working with bipolar, let alone how bipolar disorder is developed. However, new evidence has come to light about lithium’s mechanisms, specifically on the enzyme Glycogen synthase kinase 3 (GSK-3), that may open the door to understanding this disease and why lithium works so well.
GSK-3 has also been shown to play roles in a number of diseases other than bipolar, such as Alzheimer’s, Type II diabetes, and a few forms of cancer. So this research involving GSK-3 could provide many therapeutic treatments.
Lithium, a monovalent ion with a positive charge, has now been shown to have neuroprotective and neurotrophic, or cell survival, effects. This is believed to stem from the direct inhibition of GSK-3, along with a few other mechanisms.
When GSK-3 is active it is central to a number of signaling pathways, including cellular proliferation, inflammation, and apoptosis or cell death. GSK-3 activity is regulated by a wide variety of kinases, one in particular is Akt. Lithium essentially activates Akt by allowing it to complex with other proteins and be phosphorylated. Active Akt will then go on to inhibit GSK-3 by dephosphorylating it. Inhibition of GSK-3 down regulates the activity of the proliferation, inflammation and apoptotic pathways. Also, by inactivating GSK-3, a number of genes that promote neuroprotection are able to be transcribed, since they are inhibited by active GSK-3.
This would be considered a good thing in regards to neurodegenerative disorders like Alzheimer’s because this would prevent the continuation of neuronal cell death, hence the neuroprotective and neurotrophic effects of lithium.
Based on this research Lithium can have potential therapeutic effects for a number of diseases, such as bipolar, stroke, Huntington’s disease, Alzheimer’s disease, Parkinson’s disease, Retinal degeneration, Fragile X syndrome, Amyotrophic lateral sclerosis (ALS), Multiple sclerosis (MS), spinal cord injuries, HIV infections, Prion disease, alcohol-induced neurodegeneration, Down syndrome, Tardive dyskinesia, and Schizophrenia, and I’m sure the list will grow as more research is done. Lithium has been shown in a variety of animal models to treat, or at least slow the progression of many of these diseases. This extensive list should be a great motivator to continue research on lithium’s mechanism and its therapeutic properties.
But is lithium too good to be true?
It is too early to tell. There needs to be many more animal models for some of these diseases being treated with lithium before we can really see what kind of effect lithium will have in humans. Even though lithium has been used for the last 60 years to treat Bipolar disorder, its true effects on healthy humans aren’t entirely known, and there is a lot of research left to be done.
However, it is exciting to think that a therapy has been sitting under our noses for half a century, and now it may make its entrance as an invaluable part of many treatment plans. There is still a lot of the mystery yet to uncover, but hopefully it will work as a motivation.
More information on Lithium (how it is prescribed now and it’s side effects):
http://www.webmd.com/vitamins-supplements/ingredientmono-1065-LITHIUM.aspx?activeIngredientId=1065&activeIngredientName=LITHIUM
Mystery and Motivation
