"Blood Proteins Attack the Brain"...First Identification of Cerebellar Ataxia Aggravation Pathway [Reading Science]

Kyungpook National University Research Team Identifies Blood-Brain Barrier Breakdown Leading to Neuroinflammation
Offers Clues for New Therapeutic Strategies

A new inflammation-inducing pathway that exacerbates the rare degenerative brain disease known as cerebellar ataxia has been identified by a domestic research team. With the discovery that blood-derived proteins can enter the brain and trigger inflammation, this finding is being evaluated as a new potential approach for treating intractable brain disorders.

The National Research Foundation of Korea announced on the 27th that a research team led by Professor Sangryong Kim at Kyungpook National University, in collaboration with the Korea Research Institute of Chemical Technology and the Korea Brain Research Institute, has discovered that blood-derived proteins accumulate in the cerebellum of cerebellar ataxia patients and animal models, leading to neuroinflammation and cellular damage.

Blood-derived protein accumulation and pathological changes caused by blood-brain barrier damage in the cerebellum of Spinocerebellar Ataxia Type 2 (SCA2). Increased blood proteins, disruption of the blood-brain barrier, and accumulation of these proteins in the cerebellum were observed in patients with cerebellar ataxia and animal models. This process led to inflammatory responses, neuronal damage, and impaired motor function. The research team demonstrated that these pathological changes can be alleviated through caffeine and the anticoagulant rivaroxaban. Illustration and explanation: Professor Sangryong Kim, Kyungpook National University

Cerebellar ataxia is a representative degenerative brain disease caused by cerebellar dysfunction, resulting in loss of balance, gait disturbance, and impaired speech. In particular, Spinocerebellar Ataxia Type 2, which arises from genetic factors, currently lacks any fundamental treatment capable of halting disease progression.

The research team shifted focus from the traditional gene-centric approach and instead examined damage to the blood-brain barrier. The blood-brain barrier acts as a shield to prevent substances in the blood from entering the brain, but if this barrier is compromised, external substances can infiltrate the brain.

Analysis of patient blood samples confirmed elevated levels of the coagulation-related proteins thrombin and prothrombin kringle-2 (pKr-2). In subsequent animal model experiments, damage to the blood-brain barrier allowed these proteins to enter and accumulate in the cerebellum, which in turn activated microglia, leading to neuroinflammation and neuronal damage.

The researchers also presented possible therapeutic approaches. They found that strengthening blood-brain barrier function with caffeine administration, or suppressing the production of these proteins with the anticoagulant rivaroxaban, both significantly alleviated neuroinflammation and motor dysfunction.

Conversely, artificially increasing the levels of these proteins exacerbated inflammation and neuronal damage. This result demonstrates that the accumulation of blood-derived proteins is a key factor in disease progression.

Professor Sangryong Kim, who led the research, stated, "We have confirmed that cerebellar ataxia is not simply a genetic disorder, but is also closely associated with blood-brain barrier damage and the accumulation of blood proteins," adding, "This may contribute to the development of early diagnostic biomarkers and preventive treatment strategies."

This study was conducted with support from the Ministry of Science and ICT and the National Research Foundation of Korea, and was published on April 16 in the international journal 'Journal of Neuroinflammation,' which focuses on immunology and neuroscience.

This content was produced with the assistance of AI translation services.