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<p>While progress has been made in transcriptomic profiling of the human brain, functional characterization of brain regions and their interactions on the basis of regional protein expression remains limited. Here, we constructed a proteomic map from thirteen anatomical brain regions of eight cadaver donors to elucidate region-specific protein expression patterns and their implications for brain function. The results underscore the interconnectivity of the four cerebral lobes, suggesting facilitated information integration through large-scale neural networks. We propose a three-module framework (cortical integration module [frontal lobe, temporal lobe, parietal lobe, occipital lobe], limbic-relay network [amygdaloid nucleus, hippocampus, thalamus/hypothalamus], and midline regulatory axis [thalamus/hypothalamus, corpus callosum, ventricles, optic chiasm]) and provide molecular evidence supporting the potential involvement of the midline regulatory axis, brainstem, and cerebellum in higher-order cognitive functions. The midline regulatory axis may play a critical but underexplored role in neurodevelopment, interregional signaling, and structural homeostasis, potentially through efficient synaptic function, energy metabolism, and extracellular matrix integrity. This analysis may enhance the understanding of brain physiology and highlight the need to integrate proteomic and transcriptomic approaches in the study of brain function and neurological disorders.</p>

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Region-resolved proteomic map of the human brain: functional interconnections and neurological implications

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月4日

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  • Pei-Pei Zhang,
  • Man-Sheng Li,
  • Jia Zhou,
  • Chu-Hong Zhu,
  • Rui Tang,
  • Zhi-Cheng He,
  • Xiao-Hong Yao,
  • Yi-Fang Ping,
  • Dong-Fang Xiang,
  • Le-Yong Tan,
  • Yu-Jie Wang,
  • Shuai Wang,
  • Si-Si Li,
  • Jie Ma,
  • Yun-Ping Zhu,
  • Xiu-Wu Bian,
  • Ling Leng

摘要

While progress has been made in transcriptomic profiling of the human brain, functional characterization of brain regions and their interactions on the basis of regional protein expression remains limited. Here, we constructed a proteomic map from thirteen anatomical brain regions of eight cadaver donors to elucidate region-specific protein expression patterns and their implications for brain function. The results underscore the interconnectivity of the four cerebral lobes, suggesting facilitated information integration through large-scale neural networks. We propose a three-module framework (cortical integration module [frontal lobe, temporal lobe, parietal lobe, occipital lobe], limbic-relay network [amygdaloid nucleus, hippocampus, thalamus/hypothalamus], and midline regulatory axis [thalamus/hypothalamus, corpus callosum, ventricles, optic chiasm]) and provide molecular evidence supporting the potential involvement of the midline regulatory axis, brainstem, and cerebellum in higher-order cognitive functions. The midline regulatory axis may play a critical but underexplored role in neurodevelopment, interregional signaling, and structural homeostasis, potentially through efficient synaptic function, energy metabolism, and extracellular matrix integrity. This analysis may enhance the understanding of brain physiology and highlight the need to integrate proteomic and transcriptomic approaches in the study of brain function and neurological disorders.