Lithium and Autophagy

Abstract

Lithium, a drug used to treat bipolar disorders, has a variety of neuroprotective mechanisms, including autophagy regulation, in various neuropsychiatric conditions. In neurodegenerative diseases, lithium enhances degradation of aggregate-prone proteins, including mutated huntingtin, phosphorylated tau, and α-synuclein, and causes damaged mitochondria to degrade, while in a mouse model of cerebral ischemia and Alzheimer's disease autophagy downregulation by lithium is observed. The signaling pathway of lithium as an autophagy enhancer might be associated with the mammalian target of rapamycin (mTOR)-independent pathway, which is involved in myoinositol-1,4,5-trisphosphate (IP 3 ) in Huntington's disease and Parkinson's disease. However, the mTOR-dependent pathway might be involved in inhibiting glycogen synthase kinase-3β (GSK3β) in other diseases. Lithium's autophagy-enhancing property may contribute to the therapeutic benefit of patients with neuropsychiatric disorders.

Countervailing, time-dependent effects on host autophagy promote intracellular survival of Leishmania

“…Support for this hypothesis came from our previous finding of reduced IP3 levels in cells infected with L. donovani (34). In the present report, we selected inositol monophosphatase (IMPase) for study as this key enzyme is involved in inositol recycling and de novo synthesis of inositides (8,56). We reasoned that if the activity of this enzyme is reduced in leishmania infected cells, then this would result in reduced cellular inositides and lead to induction of autophagy.…”

Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

“…Additionally, here we underscore the effect of Li on the phosphorylation of mTOR, which is associated with autophagy. Autophagy plays critical roles in neuropsychiatric diseases and Li enhances autophagy via both M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 13 mTOR-independent and -dependent pathway [40]. Considering the complexity of autophagy, a much closer examination is needed in the future.…”

Genetics and Pharmacology of Longevity

“…Another compound reported to modulate autophagy is lithium (Motoi, Shimada, Ishiguro, & Hattori, 2014). Lithium is a drug approved for the treatment of bipolar disorder (BPD) and is indeed the most widely prescribed drug in neuropsychiatry for the treatment of mood disorders (Freeman & Freeman, 2006;Young & Newham, 2006).…”