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<p>The Sonic Hedgehog (SHH) signaling pathway plays a pivotal role in the development of the central nervous system (CNS), particularly in the specification and differentiation of motor neurons (MNs) from human embryonic stem cells (hESCs). Beyond early developmental processes, SHH signaling contributes to the maintenance of neuronal identity and modulates cellular responses in the adult spinal cord and brain. Dysregulation of SHH has been implicated in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Parkinson’s disease, where it influences glial activation, neuroinflammation, and neuronal survival. This review summarizes the molecular mechanisms by which SHH regulates MN formation and highlights its emerging relevance in the pathogenesis and potential treatment of neurodegenerative disorders. A deeper understanding of SHH signaling in both developmental and disease contexts may pave the way for novel therapeutic strategies in regenerative medicine and neuroprotection.</p>

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The role of Sonic Hedgehog (SHH) in the formation of motor neurons and neurodegenerative diseases

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月8日

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  • Mojtaba Esmaeli,
  • Maryam Dehghanpour Dehabadi,
  • Ali Ghanbari,
  • Forough Sadat Azimi Yancheshmeh

摘要

The Sonic Hedgehog (SHH) signaling pathway plays a pivotal role in the development of the central nervous system (CNS), particularly in the specification and differentiation of motor neurons (MNs) from human embryonic stem cells (hESCs). Beyond early developmental processes, SHH signaling contributes to the maintenance of neuronal identity and modulates cellular responses in the adult spinal cord and brain. Dysregulation of SHH has been implicated in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Parkinson’s disease, where it influences glial activation, neuroinflammation, and neuronal survival. This review summarizes the molecular mechanisms by which SHH regulates MN formation and highlights its emerging relevance in the pathogenesis and potential treatment of neurodegenerative disorders. A deeper understanding of SHH signaling in both developmental and disease contexts may pave the way for novel therapeutic strategies in regenerative medicine and neuroprotection.