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Beneficial synergistic effects of microdose lithium with pyrroloquinoline quinone in an Alzheimer's disease mouse model.
Neurobiol Aging. 2014 Dec; 35(12):2736-2745.NA

Abstract

Alzheimer's disease (AD) is a complicated, neurodegenerative disorder involving multifactorial pathogeneses and still lacks effective clinical treatment. Recent studies show that lithium exerts disease-modifying effects against AD. However, the intolerant side effects at conventional effective dosage limit the clinical use of lithium in treating AD. To explore a novel AD treatment strategy with microdose lithium, we designed and synthesized a new chemical, tri-lithium pyrroloquinoline quinone (Li3PQQ), to study the synergistic effects of low-dose lithium and pyrroloquinoline quinone, a native compound with powerful antioxidation and mitochondrial amelioration. The results showed that Li3PQQ at a relative low dose (6 and 12 mg/kg) exhibited more powerful effects in restoring the impairment of learning and memory, facilitating hippocampal long-term potentiation, and reducing cerebral amyloid deposition and phosphorylated tau level in APP/PS1 transgenic mice than that of lithium chloride at both low and high dose (5 and 100 mg/kg). We further found that Li3PQQ inhibited the activity of glycogen synthase kinase-3 and increased the activity of β-amyloid-binding alcohol dehydrogenase, which might underlie the beneficial effects of Li3PQQ on APP/PS1 transgenic mice. Our study demonstrated the efficacy of a novel AD therapeutic strategy targeting at multiple disease-causing mechanisms through the synergistic effects of microdose lithium and pyrroloquinoline quinone.

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Authors+Show Affiliations

Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.

Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.

State Key Laboratory of Medical Neurobiology, Institute of Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.

Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.

Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China; State Key Laboratory of Medical Neurobiology, Institute of Brain Science, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: zhongcj@163.com.

Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

MeSH

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsAntidepressive AgentsAntioxidantsDisease Models, AnimalDose-Response Relationship, DrugDrug SynergismDrug Therapy, CombinationGlycogen Synthase Kinase 3LearningLithium CompoundsLong-Term PotentiationMemoryMice, TransgenicPyrrolesQuinolinestau Proteins

Pub Type(s)

Journal Article

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25018109

Citation

Zhao, Lei, et al. "Beneficial Synergistic Effects of Microdose Lithium With Pyrroloquinoline Quinone in an Alzheimer's Disease Mouse Model." Neurobiology of Aging, vol. 35, no. 12, 2014, pp. 2736-2745.

Zhao L, Gong N, Liu M, et al. Beneficial synergistic effects of microdose lithium with pyrroloquinoline quinone in an Alzheimer's disease mouse model. Neurobiol Aging. 2014;35(12):2736-2745.

Zhao, L., Gong, N., Liu, M., Pan, X., Sang, S., Sun, X., Yu, Z., Fang, Q., Zhao, N., Fei, G., Jin, L., Zhong, C., & Xu, T. (2014). Beneficial synergistic effects of microdose lithium with pyrroloquinoline quinone in an Alzheimer's disease mouse model. Neurobiology of Aging, 35(12), 2736-2745. https://doi.org/10.1016/j.neurobiolaging.2014.06.003

Zhao L, et al. Beneficial Synergistic Effects of Microdose Lithium With Pyrroloquinoline Quinone in an Alzheimer's Disease Mouse Model. Neurobiol Aging. 2014;35(12):2736-2745. PubMed PMID: 25018109.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Beneficial synergistic effects of microdose lithium with pyrroloquinoline quinone in an Alzheimer's disease mouse model. AU - Zhao,Lei, AU - Gong,Neng, AU - Liu,Meng, AU - Pan,Xiaoli, AU - Sang,Shaoming, AU - Sun,Xiaojing, AU - Yu,Zhe, AU - Fang,Qi, AU - Zhao,Na, AU - Fei,Guoqiang, AU - Jin,Lirong, AU - Zhong,Chunjiu, AU - Xu,Tianle, Y1 - 2014/06/14/ PY - 2013/11/05/received PY - 2014/04/27/revised PY - 2014/06/07/accepted PY - 2014/7/15/entrez PY - 2014/7/16/pubmed PY - 2015/11/10/medline KW - Alzheimer's disease KW - Glycogen synthase kinase-3 KW - Lithium KW - Pyrroloquinoline quinone KW - β-Amyloid-binding alcohol dehydrogenase SP - 2736 EP - 2745 JF - Neurobiology of aging JO - Neurobiol Aging VL - 35 IS - 12 N2 - Alzheimer's disease (AD) is a complicated, neurodegenerative disorder involving multifactorial pathogeneses and still lacks effective clinical treatment. Recent studies show that lithium exerts disease-modifying effects against AD. However, the intolerant side effects at conventional effective dosage limit the clinical use of lithium in treating AD. To explore a novel AD treatment strategy with microdose lithium, we designed and synthesized a new chemical, tri-lithium pyrroloquinoline quinone (Li3PQQ), to study the synergistic effects of low-dose lithium and pyrroloquinoline quinone, a native compound with powerful antioxidation and mitochondrial amelioration. The results showed that Li3PQQ at a relative low dose (6 and 12 mg/kg) exhibited more powerful effects in restoring the impairment of learning and memory, facilitating hippocampal long-term potentiation, and reducing cerebral amyloid deposition and phosphorylated tau level in APP/PS1 transgenic mice than that of lithium chloride at both low and high dose (5 and 100 mg/kg). We further found that Li3PQQ inhibited the activity of glycogen synthase kinase-3 and increased the activity of β-amyloid-binding alcohol dehydrogenase, which might underlie the beneficial effects of Li3PQQ on APP/PS1 transgenic mice. Our study demonstrated the efficacy of a novel AD therapeutic strategy targeting at multiple disease-causing mechanisms through the synergistic effects of microdose lithium and pyrroloquinoline quinone. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/25018109/Beneficial_synergistic_effects_of_microdose_lithium_with_pyrroloquinoline_quinone_in_an_Alzheimer's_disease_mouse_model_ DB - PRIME DP - Unbound Medicine ER -