Is There Justification to Treat Neurodegenerative Disorders by Repurposing Drugs? The Case of Alzheimer's Disease, Lithium, and Autophagy.

Odeya Damri,Nofar Shemesh,Galila Agam

doi:10.3390/ijms22010189

Abstract

Lithium is the prototype mood-stabilizer used for acute and long-term treatment of bipolar disorder. Cumulated translational research of lithium indicated the drug’s neuroprotective characteristics and, thereby, has raised the option of repurposing it as a drug for neurodegenerative diseases. Lithium’s neuroprotective properties rely on its modulation of homeostatic mechanisms such as inflammation, mitochondrial function, oxidative stress, autophagy, and apoptosis. This myriad of intracellular responses are, possibly, consequences of the drug’s inhibition of the enzymes inositol-monophosphatase (IMPase) and glycogen-synthase-kinase (GSK)-3. Here we review lithium’s neurobiological properties as evidenced by its neurotrophic and neuroprotective properties, as well as translational studies in cells in culture, in animal models of Alzheimer’s disease (AD) and in patients, discussing the rationale for the drug’s use in the treatment of AD.

Highlights

Neurodegeneration in general relates to neuronal death in the central nervous system (CNS)
We first reviewed translational research which indicates the drug’s neuroprotective characteristics, namely, its neurobiological properties as evidenced by its neurotrophic and neuroprotective effects culminating in modulation of homeostatic mechanisms, such as inflammation, mitochondrial function, oxidative stress, autophagy and apoptosis
We summarized that the myriad of intracellular responses is, possibly, a consequence of the drug’s inhibition of the enzymes IMPase and GSK-3

Summary

Introduction

Neurodegeneration in general relates to neuronal death in the central nervous system (CNS). Neurodegenerative diseases are characterized by gradual anatomical and/or physiological aberration of neuronal systems. They include Huntington’s disease (HD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) [1]. As of now-a-days all neurodegenerative diseases are clinically unmanageable. This situation might get worse as the aging population is increasing worldwide. We briefly review the different types of neurodegenerative diseases and successful or unsuccessful treatment avenues with emphasis on AD. We review and discuss pros and cons to repurpose lithium salts (lithium), the prototype drug for bipolar disorder, for the treatment of AD

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Methods

Conclusion