Huntingtin and its allies at the cortico-striatal synapse

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Huntington's Disease (HD) is a neurodegenerative disorder marked by progressive motor and cognitive decline.
• Cortico-striatal synaptic dysfunction is a primary driver of HD pathology.
• Huntingtin (HTT) protein is crucial for synaptic function, located at both pre- and postsynaptic sites.

Purpose of the Study:

• To review 30 years of research on huntingtin protein's synaptic interactors.
• To focus on experimentally validated HTT-interacting proteins (HIPs).
• To elucidate the role of HIPs in cortico-striatal synaptic dysfunction in HD.

Main Methods:

• Literature review of studies investigating HTT protein interactions.
• Analysis of experimentally validated pre- and postsynaptic partners of HTT.
• Synthesis of findings related to HIPs' function in synaptic integrity and HD.

Main Results:

• HTT is a central scaffold protein at synapses, regulating vesicle cycling and receptor dynamics.
• A growing network of HTT-interacting proteins (HIPs) has been identified.
• These HIPs are critical for maintaining synaptic structure and function, and their dysfunction is implicated in HD.

Conclusions:

• Huntingtin protein is integral to synaptic integrity through its interactions with numerous partners.
• Dysregulation of HTT-interacting proteins contributes significantly to cortico-striatal synaptic dysfunction in Huntington's Disease.
• Understanding these interactions is key to developing therapeutic strategies for HD.