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<p>Huntington’s Disease (HD) is characterized by progressive motor and cognitive decline, largely driven by cortico-striatal synaptic dysfunction. Central to these processes is huntingtin (HTT) protein, which is abundantly present at the synapse. HTT regulates the synaptic vesicle cycle at presynaptic terminals and serves as a scaffold at the postsynaptic density where it modulates receptor dynamics. An expanding network of HTT-interacting proteins (HIPs), crucial for maintaining synaptic structure and function, underscores the role of HTT as a core component of synaptic integrity. This review examines the 30-year research journey that has unveiled HTT pre- and postsynaptic partners, with focus on experimentally validated interactors and their involvement in HD cortico-striatal synaptic dysfunction.</p>

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Huntingtin and its allies at the cortico-striatal synapse

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月27日

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  • Chiara Zuccato,
  • Andrea Scolz,
  • Raffaele Iennaco

摘要

Huntington’s Disease (HD) is characterized by progressive motor and cognitive decline, largely driven by cortico-striatal synaptic dysfunction. Central to these processes is huntingtin (HTT) protein, which is abundantly present at the synapse. HTT regulates the synaptic vesicle cycle at presynaptic terminals and serves as a scaffold at the postsynaptic density where it modulates receptor dynamics. An expanding network of HTT-interacting proteins (HIPs), crucial for maintaining synaptic structure and function, underscores the role of HTT as a core component of synaptic integrity. This review examines the 30-year research journey that has unveiled HTT pre- and postsynaptic partners, with focus on experimentally validated interactors and their involvement in HD cortico-striatal synaptic dysfunction.