title: Lithium and autophagy.
abstract: Lithium, a drug used to treat bipolar disorders, has a variety of neuroprotective mechanisms, including autophagy regulation, in various neuropsychiatric conditions. In neurodegenerative diseases, lithium enhances degradation of aggregate-prone proteins, including mutated huntingtin, phosphorylated tau, and α-synuclein, and causes damaged mitochondria to degrade, while in a mouse model of cerebral ischemia and Alzheimer's disease autophagy downregulation by lithium is observed. The signaling pathway of lithium as an autophagy enhancer might be associated with the mammalian target of rapamycin (mTOR)-independent pathway, which is involved in myo-inositol-1,4,5-trisphosphate (IP3) in Huntington's disease and Parkinson's disease. However, the mTOR-dependent pathway might be involved in inhibiting glycogen synthase kinase-3β (GSK3β) in other diseases. Lithium's autophagy-enhancing property may contribute to the therapeutic benefit of patients with neuropsychiatric disorders.
authors.affiliation: †Department of Diagnosis, Prevention and Treatment of Dementia, ‡Department of Neurology, and §Department of Pharmacy, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Motoi
authors.affiliation: †Department of Diagnosis, Prevention and Treatment of Dementia, ‡Department of Neurology, and §Department of Pharmacy, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Shimada
authors.affiliation: †Department of Diagnosis, Prevention and Treatment of Dementia, ‡Department of Neurology, and §Department of Pharmacy, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ishiguro
authors.affiliation: †Department of Diagnosis, Prevention and Treatment of Dementia, ‡Department of Neurology, and §Department of Pharmacy, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D006801:Humans; D018020:Lithium Compounds / Q000494:pharmacology*; D009422:Nervous System Diseases / Q000188:drug therapy / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*
chemical_list: D018020:Lithium Compounds; D018696:Neuroprotective Agents
keywords: GSK3β, IMPase; Huntingtin; Lithium; autophagy; prion protein; tau; α-synuclein
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