Scholarlink

Background <p>Macrophage lipid accumulation is a hallmark of atherosclerosis and other metabolic diseases. Toll-like receptor 4 (TLR4) signaling and cytoskeletal remodeling have each been implicated in this process, yet the mechanistic connections among these three elements remain incompletely defined.</p> Main body <p>This review synthesizes current evidence for pathways in which TLR4 activation, via bifurcated signaling through MyD88/TRAM, SYK/Src, and integrins, engages small GTPases (Rac, Cdc42, Rho) and downstream effectors including cofilin and paxillin to drive cytoskeletal remodeling. These cytoskeletal changes facilitate lipid internalization through multiple routes, including macropinocytosis, receptor redistribution, and lysosomal synapse formation, and regulate lipid droplet dynamics, ultimately promoting foam cell formation. We also discuss the therapeutic potential and safety challenges of targeting cytoskeletal regulators in diseases such as atherosclerosis.</p> Short conclusion <p>The convergence of TLR4 signaling, cytoskeletal remodeling, and lipid metabolism represents a compelling mechanistic nexus for understanding foam cell formation. Elucidating the molecular details of this pathway—particularly the SYK/Src-cytoskeleton axis—may reveal macrophage-selective therapeutic targets that suppress pathological lipid accumulation while preserving host defense functions.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Toll-like receptor 4 signaling links cytoskeletal remodeling to lipid accumulation in macrophages

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月4日

查看全文
  • En Wang,
  • Hamizah Shahirah Hamezah,
  • Rongchun Han,
  • Xiaohui Tong

摘要

Background

Macrophage lipid accumulation is a hallmark of atherosclerosis and other metabolic diseases. Toll-like receptor 4 (TLR4) signaling and cytoskeletal remodeling have each been implicated in this process, yet the mechanistic connections among these three elements remain incompletely defined.

Main body

This review synthesizes current evidence for pathways in which TLR4 activation, via bifurcated signaling through MyD88/TRAM, SYK/Src, and integrins, engages small GTPases (Rac, Cdc42, Rho) and downstream effectors including cofilin and paxillin to drive cytoskeletal remodeling. These cytoskeletal changes facilitate lipid internalization through multiple routes, including macropinocytosis, receptor redistribution, and lysosomal synapse formation, and regulate lipid droplet dynamics, ultimately promoting foam cell formation. We also discuss the therapeutic potential and safety challenges of targeting cytoskeletal regulators in diseases such as atherosclerosis.

Short conclusion

The convergence of TLR4 signaling, cytoskeletal remodeling, and lipid metabolism represents a compelling mechanistic nexus for understanding foam cell formation. Elucidating the molecular details of this pathway—particularly the SYK/Src-cytoskeleton axis—may reveal macrophage-selective therapeutic targets that suppress pathological lipid accumulation while preserving host defense functions.