黑料吃瓜资源

Imagine you wake up in a hospital without a single memory of the last month. Doctors say you had a series of violent episodes and paranoid delusions. You鈥檇 become convinced you were suffering from bipolar disorder. Then, after a special test, a neurologist diagnoses you with a rare autoimmune disease called anti-NMDAR encephalitis. This is what happened to Susannah Cahalan, a New York Post reporter who would go on to write the best-selling memoir Brain on Fire: My Month of Madness.

Anti-NMDAR encephalitis can lead to hallucinations, blackouts, and psychosis, says 黑料吃瓜资源 Professor Hiro Furukawa. It mostly affects women ages 25 to 35鈥攖he same age at which schizophrenia often presents itself. But what鈥檚 happening in anti-NMDAR encephalitis is something else.

Furukawa specializes in NMDARs, brain receptors that play a critical role in cognition and memory. 鈥淚n anti-NMDAR encephalitis, antibodies bind to those receptors and prevent them from working,鈥� he explains. As an autoimmune response, the brain becomes inflamed鈥攈ence, Brain on Fire.

While some treatments are available, their effectiveness varies depending on symptom severity. New research from the Furukawa lab may explain why. In a recent study, Furukawa and colleagues map how antibodies from three patients bind to NMDARs. They find that the way in which each of the three antibodies binds to NMDARs differs. The discovery marks an important step in gaining a fuller understanding of anti-NMDAR encephalitis, a condition first diagnosed in 2008. Furthermore, it suggests personalized medicine may be critical for treating this disease.

鈥淒istinct binding patterns manifest in different functional regulation levels in NMDARs,鈥� Furukawa explains. 鈥淭his affects neuronal activities. So, different binding sites may correspond to variations in patients鈥� symptoms.鈥� Uncovering those correlations could lead to more precise therapeutic strategies. Imagine, for example, that scientists identify several binding sites common among encephalitis patients. Pharmacologists could then design new drugs to target these sites. But that鈥檚 not all. Personalized medicine could also mean more accurate diagnoses, Furukawa says.

鈥淚t鈥檚 still a rare disease, but it could be misdiagnosed or underdiagnosed. Therefore, we need to spread awareness. Could, for example, some schizophrenic patients have this disease? Could it be caused by antibodies?鈥�

Currently, it鈥檚 said that anti-NMDAR encephalitis affects one in 1.5 million people. Yet, in time, we may find it鈥檚 more common than previously assumed. That鈥檚 a scary thought. However, it could explain why existing psychiatric medicine does not work for some people diagnosed with bipolar disorder and other mental health conditions鈥攁 huge revelation for patients as well as the families and therapists who care for them.

Written by: Jen A. Miller | [email protected] | 516-367-8455

Funding

National Institutes of Health, Austin鈥檚 Purpose, Robertson Research Fund, Doug Fox Alzheimer鈥檚 Fund, Heartfelt Wings Foundation, Gertrude and Louis Feil Family Trust, German Research Foundation, German Federal Ministry of Education and Research, Schilling Foundation

Citation

Michalski, K., et al., 鈥淪tructural and functional mechanisms of anti-NMDAR autoimmune encephalitis鈥�, Nature Structural & Molecular Biology, September 3, 2024. DOI:

Jain, A., et al., 鈥淒endritic, delayed, stochastic CaMKII activation in behavioural time scale plasticity鈥�, Nature, October 9, 2024. DOI:

Core Facilites

鈥淭丑别 Electron Cryomicroscopy (Cryo-EM) Facility offers researchers access to cutting-edge technology that has made it possible to visualize complex biological systems at near atomic resolution and detail, providing novel molecular insight into human biology and disease.鈥� 鈥� Cryo-EM Facility Manager Dennis Thomas