lithium-chloride and Movement-Disorders

Topics: Antimanic Agents; Bipolar Disorder; Humans; Lithium Chloride; Male; Middle Aged; Movement Disorders; Posture; Video Recording

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucelotide repeat that encodes an abnormal polyglutamine (PolyQ) tract in the disease protein, ataxin-3. The formation of neuronal intranuclear inclusions in the specific brain regions is one of the pathological hallmarks of SCA3. Acceleration of the degradation of the mutant protein aggregates is proven to produce beneficial effects in SCA3 and other PolyQ diseases. Lithium is known to be neuroprotective in various models of neurodegenerative disease and can reduce the mutant protein aggregates by inducing autophagy. In this study, we explored the therapeutic potential of lithium in a SCA3 Drosophila model. We showed that chronic treatment with lithium chloride at specific doses notably prevented eye depigmentation, alleviated locomotor disability, and extended the median life spans of SCA3 transgenic Drosophila. By means of genetic approaches, we showed that co-expressing the mutant S9E, which mimicked the phosphorylated S9 state of Shaggy as done by lithium, also partly decreased toxicity of gmr-SCA3tr-Q78. Taken together, our findings suggest that lithium is a promising therapeutic agent for the treatment of SCA3 and other PolyQ diseases.

Topics: Age Factors; Animals; Animals, Genetically Modified; Ataxin-3; Disease Models, Animal; Dose-Response Relationship, Drug; Drosophila; Enzyme Activation; Eye; Gene Expression Regulation; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Humans; Lithium Chloride; Microscopy, Electron, Scanning; Motor Activity; Movement Disorders; Nerve Tissue Proteins; Neurodegenerative Diseases; Neuroprotective Agents; Nuclear Proteins; Peptides; Repressor Proteins