Neuroprotective Effects of Lithium: Implications for the Treatment of Alzheimer’s Disease and Related Neurodegenerative Disorders

Abstract

Lithium is a well-established therapeutic option for the acute and long-term management of bipolar disorder and major depression. More recently, based on findings from translational research, lithium has also been regarded as a neuroprotective agent and a candidate drug for disease-modification in certain neurodegenerative disorders, namely, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and, more recently, Parkinson's disease (PD). The putative neuroprotective effects of lithium rely on the fact that it modulates several homeostatic mechanisms involved in neurotrophic response, autophagy, oxidative stress, inflammation, and mitochondrial function. Such a wide range of intracellular responses may be secondary to two key effects, that is, the inhibition of glycogen synthase kinase-3 beta (GSK-3β) and inositol monophosphatase (IMP) by lithium. In the present review, we revisit the neurobiological properties of lithium in light of the available evidence of its neurotrophic and neuroprotective properties, and discuss the rationale for its use in the treatment and prevention of neurodegenerative diseases.

Modulation of GPCRs by monovalent cations and anions

“…While only Na + and K + physiologically modulate GPCR function, the latter three cations provide extremely valuable tools for the analysis of ion effects on GPCRs because they differ from each other in physicochemical properties (Table 2). Moreover, Li + is unique in this series because this cation is highly effective in the treatment of manic-depressive (bipolar) disorders (Beaulieu et al 2009;Marlinge et al 2014;Tselnicker et al 2014) and there is recent interest in Li + as drug for the treatment of neurodegenerative diseases (Forlenza et al 2014). Although the concentrations at which the Li + affects GPCR function in vitro are much higher than the therapeutic plasma concentrations in patients (∼1 mM) (Grandjean and Aubry 2009), it cannot be excluded that Li + interacts with GPCRs in vivo.…”

Biological effects of lithium – fundamental and medical aspects

“…Now it is known that lithium exhibits therapeutic effect in treatment of some neurological disea ses such as Alzheimer's disease (AD), Parkinson's disea se (PD) [21], amyotrophic lateral sclerosis [22]. Lithium may alter the biochemical processes that determine the pathogenesis of these diseases.…”

Neurotrophic effects of lithium stimulate the reduction of ischemic and neurodegenerative brain damage

“…В эксперименте было показано, что литий уменьшает по-веденческие и когнитивные нарушения в животных моде-лях нейродегенеративных заболеваний, таких как ин-сульт, боковой амиотрофический склероз (БАС), синдром ломкой Х-хромосомы, болезнь Гентингтона (БГ), БА, бо-лезнь Паркинсона [44].…”