Lithium engages autophagy for neuroprotection and neuroplasticity: Translational evidence for therapy

Here an overview is provided on therapeutic/neuroprotective effects of Lithifum (Li⁺) in neurodegenerative and psychiatric disorders focusing on the conspicuous action of Li⁺ through autophagy. The effects on the autophagy machinery remain the key molecular mechanisms to explain the protective effects of Li⁺ for neurodegenerative diseases, offering potential therapeutic strategies for the treatment of neuropsychiatric disorders and emphasizes a crossroad linking autophagy, neurodegenerative disorders, and mood stabilization. Sensitization by psychostimulants points to several mechanisms involved in psychopathology, most also crucial in neurodegenerative disorders. Evidence shows the involvement of autophagy and metabotropic Glutamate receptors-5 (mGluR5) in neurodegeneration due to methamphetamine neurotoxicity as well as in neuroprotection, both in vitro and in vivo models. More recently, Li⁺ was shown to modulate autophagy through its action on mGluR5, thus pointing to an additional way of autophagy engagement by Li⁺ and to a substantial role of mGluR5 in neuroprotection related to neural e neuropsychiatry diseases. We propose Li⁺ engagement of autophagy through the canonical mechanisms of autophagy machinery and through the intermediary of mGluR5.