Beneficial synergistic effects of microdose lithium with pyrroloquinoline quinone in an Alzheimer's disease mouse model

Lei Zhao, Neng Gong, Meng Liu, Xiaoli Pan, Shaoming Sang, Xiaojing Sun, Zhe Yu, Qi Fang, Na Zhao, Guoqiang Fei, Lirong Jin, Chunjiu Zhong, Tianle Xu

Research output: Contribution to journalArticlepeer-review

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 12mg/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 100mg/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.

Original languageEnglish (US)
Pages (from-to)2736-2745
Number of pages10
JournalNeurobiology of aging
Volume35
Issue number12
DOIs
StatePublished - Dec 1 2014

Keywords

  • Alzheimer's disease
  • Glycogen synthase kinase-3
  • Lithium
  • Pyrroloquinoline quinone
  • β-Amyloid-binding alcohol dehydrogenase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology

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