Lithium-induced neuroprotection in bipolar disorder: Translational insights into cytoskeletal and proteomic mechanisms.

The pharmacotherapy of lithium plays mainstay in the modulation of bipolar disorder (BD) and controls other neuropsychiatric conditions such as prophylactic and mood episodes. However, its neurotrophic properties embrassing hypothetically converged synaptic regulation to BD remains elusive. Several studies intricate evidence of lithium targetting 'microtubular associated protein-2 (MAP2)' to endure neuroprotection. Synthesis of multiple single nucleiotide gene polymorphisms of Snap-25 gene is considered a milestone in MAP2 alteration. In fact, upregulated NAA (N-acetyl-aspartate), oxidative stess, and neurotrophins can cause neuronal vulnerability. Proteomic data from animal models and human samples exhibited evidence of cytoskeletal proteins associated lithium-dependent neural plasticity. Recent findings emphasized significance on lithium controlling Akt and GSK3 inhibition as a crucial mechanism to promote neuroprotection. As a therapeutic regimen to BD, lithium targets gene expression regulation and post-translational modification pathways. Therefore this narrative review intent to summarise a comprehensive understanding of neurotrophic effects of lithium via diverse signaling pathways. Considering these steps we propose that the therapeutic effect of lithium can particularly modulate any one subtype of BD during the onset of sensitization. This scheme can further assist whether molecular pathways involving cytoskeletal regulation are amendable to treat BD. The review will also highlight stratified chemical pathways by which lithium action as an effective mood-stabilizing agent to exert its association with neural plasticity.