Thu, Feb 18, 2016 page5

• Researchers make gene breakthrough

  DISORDER: The team found that a process known as SUMOylation can help battle mutation of a gene responsible for 90 percent of Rett syndrome cases

  • By Chen Wei-han / Staff reporter
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  Academia Sinica researchers have discovered that modification of a gene known to often be mutated in people with the neurological disorder Rett syndrome could ameliorate the behavioral deficits of social interaction, memory impairment and neuron degeneration.

  Rett syndrome is a rare neuro-developmental disorder that first became well known through the film Silent Angels: The Rett Syndrome Story in 2000. It occurs in about one in 10,000 female births, while boys with this disorder normally do not survive.

  Children with Rett syndrome usually develop deficits in motor function, social ability, learning and memory performance, and emotional control. The disorder is incurable, with drugs only able to alleviate symptoms.

  Rett syndrome is closely linked to the MECP2 gene, the mutation of which is responsible for more than 90 percent of cases of the disease, Academia Sinica research fellow Eminy Hsiao-yuan Lee (李小媛) said.

  The team discovered that the MeCP2 protein is modified by small ubiquitin-like modifier (SUMO) proteins — a family of small proteins that are attached to and detached from other proteins to modify their function — and the process, called SUMOylation, can rescue the behavioral and neural deficits in MeCP2 knockout mice, Lee said.

  Abnormal levels of MeCP2 SUMOylation are associated with social and behavioral deficits, while the team observed a consistent and significant decrease in MeCP2 SUMOylation in Rett syndrome patients.

  “That MeCP2 undergoes SUMOylation and that the process affects Rett syndrome patients are a previously unknown mechanism of the disorder. The findings advance our understanding of Rett syndrome and suggest new therapeutic strategies,” Lee said.

  Increased MeCP2 SUMOylation also increases the expression of the BDNF gene, which contributes to enhancing learning and memory, neuroplasticity and protection against neurodegenerative diseases, while BDNF gene-based therapies have been used to treat Parkinson’s disease and degenerative neural disorders, she said.

  The team also found two substances naturally occurring in the human body that could significantly increase the level of MeCP2 SUMOylation in a rat’s brain: insulin-like growth factor-1 (IGF-1), which facilitates neural transmission, and corticotrophin-releasing factor (CRF), which stimulates adrenalin secretion and boosts learning and memory.

  “While few reports have shown that IGF-1 has a therapeutic effect in Rett Syndrome patients, it is the first time that CRF is demonstrated to enhance MeCP2 SUMOylation and Bdnf gene expression to facilitate learning and memory. Our research results can perhaps provide a novel direction for the therapeutic potential of steroid hormones, such as corticosterone, against Rett syndrome,” Lee said.

  The results were published earlier this month in the journal Nature Communications.
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