LMDS-1, a potential TrkB receptor agonist provides a safe and neurotrophic effect for early-phase Alzheimer’s disease

Chia Hao Fan, Chia Wei Lin, Hei Jen Huang, Guey Jen Lee-Chen, Ying Chieh Sun, Wenwei Lin, Chiung Mei Chen, Kuo Hsuan Chang, Ming Tsan Su*, Hsiu Mei Hsieh-Li*


研究成果: 雜誌貢獻期刊論文同行評審

14 引文 斯高帕斯(Scopus)


Rationale: The signaling pathways of tropomyosin-related kinase B (TrkB) receptor play a pivotal role in axonal sprouting, proliferation of dendritic arbor, synaptic plasticity, and neuronal differentiation. The levels of BDNF and TrkB receptor were reduced in patients with Alzheimer’s disease (AD). Objectives: The activation of TrkB signaling pathways is a potential strategy for AD therapies. We intended to identify potential TrkB agonists to activate the neuroprotective signaling to alleviate the pathological features of AD mice. Results: Both of the Aβ-deteriorated hippocampal primary neurons and mouse models were generated and showed AD characteristics. We first investigated 12 potential TrkB agonists with primary hippocampal neurons of mice. Both 7,8-DHF and LMDS-1 were identified to have better effect than the other compounds on dendritic arborization of the neurons and were further applied to the Aβ-injected mouse model. The short-term cognitive behavior and pathology in the mice were improved by LMDS-1. Further investigation indicated that LMDS-1 activated the TrkB through phosphorylation at Y516 rather than Y816. In addition, the ERK but not CaMKII or Akt was activated in the mouse hippocampus with LMDS-1 administration. LMDS-1 treatment also upregulated CREB and BDNF while downregulated the GSK3β active form and tau phosphorylation. Conclusions: This study suggests that LMDS-1 upregulates the expression of BDNF and ameliorates the early-phase phenotypes of the AD-like mice through the pTrkB (Y516)-ERK-CREB pathway. In addition, LMDS-1 has better effect than 7,8-DHF in ameliorating the behavioral and pathological features of AD-like mice.

頁(從 - 到)3173-3190
出版狀態已發佈 - 2020 10月 1

ASJC Scopus subject areas

  • 藥理


深入研究「LMDS-1, a potential TrkB receptor agonist provides a safe and neurotrophic effect for early-phase Alzheimer’s disease」主題。共同形成了獨特的指紋。