Details

Autor(en) / Beteiligte

• Habib, Ahsan
• Sawmiller, Darrell
• Li, Song
• Xiang, Yang
• Rongo, David
• Tian, Jun
• Hou, Huayan
• Zeng, Jin
• Smith, Adam
• Fan, Shengnuo
• Giunta, Brian
• Mori, Takashi
• Currier, Glenn
• Shytle, Douglas Ronald
• Tan, Jun

Titel

RETRACTED ARTICLE:LISPRO mitigates β-amyloid and associated pathologies in Alzheimer’s mice

Ist Teil von

• Cell death & disease, 2017-06, Vol.8 (6), p.e2880-e2880

Ort / Verlag

London: Springer Nature B.V

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Abstract Lithium has been marketed in the United States of America since the 1970s as a treatment for bipolar disorder. More recently, studies have shown that lithium can improve cognitive decline associated with Alzheimer’s disease (AD). However, the current United States Food and Drug Administration-approved lithium pharmaceutics (carbonate and citrate chemical forms) have a narrow therapeutic window and unstable pharmacokinetics that, without careful monitoring, can cause serious adverse effects. Here, we investigated the safety profile, pharmacokinetics, and therapeutic efficacy of LISPRO (ionic co-crystal of lithium salicylate and l-proline), lithium salicylate, and lithium carbonate (Li 2 CO 3 ). We found that LISPRO (8-week oral treatment) reduces β -amyloid plaques and phosphorylation of tau by reducing neuroinflammation and inactivating glycogen synthase kinase 3 β in transgenic Tg2576 mice. Specifically, cytokine profiles from the brain, plasma, and splenocytes suggested that 8-week oral treatment with LISPRO downregulates pro-inflammatory cytokines, upregulates anti-inflammatory cytokines, and suppresses renal cyclooxygenase 2 expression in transgenic Tg2576 mice. Pharmacokinetic studies indicated that LISPRO provides significantly higher brain lithium levels and more steady plasma lithium levels in both B6129SF2/J (2-week oral treatment) and transgenic Tg2576 (8-week oral treatment) mice compared with Li 2 CO 3 . Oral administration of LISPRO for 28 weeks significantly reduced β -amyloid plaques and tau-phosphorylation. In addition, LISPRO significantly elevated pre-synaptic (synaptophysin) and post-synaptic protein (post synaptic density protein 95) expression in brains from transgenic 3XTg-AD mice. Taken together, our data suggest that LISPRO may be a superior form of lithium with improved safety and efficacy as a potential new disease modifying drug for AD.