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“Sensor study identifies cause of brain dysfunction in Huntington’s disease”
A Korean research team says they have found the cause of brain dysfunction in patients with Huntington’s disease (HD).
HD is an inherited neurodegenerative disease that typically begins around age 40. It causes uncontrolled jerky body movements, personality changes and symptoms of dementia. It eventually leads to death, but there is no cure.
On Sunday, the Korea Institute of Science and Technology (KIST) said its research team, led by researchers Seong Ji-hye and Ryu Hoon of KIST’s Institute of Brain Science, found that the activity of focal adhesion kinase (FAK) was significantly reduced in the brain. tissues from HD patients. FAK plays an important role in neurite motility and normal synaptic functions.
The research team measured FAK activity in living cells using a molecular fluorescence sensor based on fluorescence resonance energy transfer (FRET) and verified it.
For normal FAK activity, phosphatidylinositol 4,5-biphosphate (PIP2) is essential among the cell membrane phospholipids.
However, in cells with HD, PIP2 was abnormally distributed, the research team said.
The research team used super-resolution structured illumination microscopy to discover that PiP2 abnormally binds mutant huntingtin (mHTT) protein and cannot be distributed normally in the cell membrane.
The abnormal distribution of PIP2 inhibited FAK activity in HD, and the reduced FAK activity disrupted normal synaptic functions. The research team said this is the cause of brain dysfunction in early HD.
“The pathological mechanism of synaptic dysfunction in HD patients, discovered in this study, can be used as a therapeutic target to recover brain dysfunction during HD progression,” Seong said.
Ryu noted that the study results demonstrated the pathological mechanism in the brains of HD patients, suggesting a new treatment target for human degenerative brain diseases.
The study, titled “Decreased FAK activity and focal adhesion dynamics impairs proper neurite formation of medium spiny neurons in Huntington’s disease,” was published in the latest issue of Acta Neuropathologica.
Reference: Lee HN, Hyeon SJ, Kim H, et al. Decreased FAK activity and focal adhesion dynamics impair proper neurite formation of medium spiny neurons in Huntington’s disease. Acta Neuropathol. 2022;144(3):521-536. do I: 10.1007/s00401-022-02462-z
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