A study headed by Academia Sinica researchers found that the instability of certain proteins might cause abnormal brain development, which was previously believed to be caused by genetic mutations.
Thus far, studies on cerebral development mainly focused on the transcriptional regulation of neurogenesis, underestimating the role of protein modification, Chen Ruey-hwa (陳瑞華), a research fellow at Academia Sinica’s Institute of Biological Chemistry, told a news conference in Taipei.
The stability of proteins is key to various bodily functions, she said.
Photo courtesy of Academia Sinica
The team, headed by Chen and Chou Shen-ju (周申如), an associate research fellow at Academica Sinica’s Institute of Cellular and Organismic Biology, found that a deubiquitinating enzyme called USP11 is related to cerebral malformation.
USP11 gene variants were previously discovered in people with inherited neurologic disorders, Chen added.
By deubiquitination, USP11 inhibits the modification of the SOX11 gene and stabilizes its expressions to facilitate neuron formation and the migration of newly synthesized neurons to their correct positions in the brain, contributing to building the brain’s neuron circuit, she said.
Ubiquitination refers to a cellular process that regulates proteins, including removing excessive or damaged proteins, and it can also repair damaged DNA, she added.
Through experiments on mice, the researcher found that USP11-deficient animals’ brains had a high number of unstable proteins, leading to the malformation of cortical development, he said.
When the USP11-deficient mice grew up, they exhibited behavioral abnormalities in, for example, learning, memory, and social and emotional expressions, she said.
The cerebral cortex is responsible for sensory and emotional processing, and higher cognitive functions, Chen said.
Its development is a dynamic and precisely orchestrated process, while any disruption during the process might lead to neurological disorders, such as intellectual disability, epilepsy or autism, she said.
People with neurological disorders often require long-term care and special education, causing considerable burden on their family and society, she said.
The study sheds light on the diagnosis and treatment of neurologic disorders related to abnormal cortical development, Chen said, adding that she hopes it would help develop methods to monitor brain development in infants.
The study, titled “Usp11 controls cortical neurogenesis and neuronal migration through SOX11 stabilization,” was published in the journal Science Advances on Friday last week.
It was partly funded by the Ministry of Science and Technology, the researchers said.
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