Brazilian scientists investigating Creutzfeldt-Jakob disease in influencer Lito Sousa have used the Sirius particle accelerator to examine how abnormal prion proteins cause brain damage.
The study, published in the scientific journal Science Advances, was conducted by researchers from the Federal University of Rio de Janeiro (UFRJ) and the National Center for Research in Energy and Materials (CNPEM).
The research gained widespread attention following the diagnosis of 59-year-old Lito Sousa, a prominent Brazilian aviation specialist whose social media channel has reached four million subscribers. In his first public interview after receiving his diagnosis, Sousa stated that he would be prepared for what lies ahead.
Creutzfeldt-Jakob disease is a rare and fatal neurological condition. Over a 16-year period, health authorities in Brazil recorded more than 1,000 suspected cases of the disease across the nation.
Particle Accelerator Technology at Sirius Facility
To conduct the study, researchers utilized the Cateretê light line at Sirius, a 68,000-square-meter particle accelerator located at the CNPEM campus in Campinas, São Paulo state.
Inaugurated in 2018, Sirius represents the largest and most complex scientific research infrastructure ever constructed in Brazil. It is also recognized as the largest particle accelerator in Latin America, generating ultra-bright synchrotron light to analyze materials at atomic and molecular scales.
The CNPEM institution operates under Brazil's Ministry of Science, Technology and Innovation, maintaining state-of-the-art laboratories for advanced interdisciplinary scientific research.
Mechanisms of Prion Diseases and Neurological Damage
Prion diseases, officially known as transmissible spongiform encephalopathies, are a rare class of neurodegenerative disorders characterized by long incubation periods that affect humans and animals.
Among the most widely recognized conditions in this category are Creutzfeldt-Jakob disease and Bovine Spongiform Encephalopathy, commonly referred to as mad cow disease.
Despite their rarity, the primary hallmark of these conditions is an ultra-rapid clinical decline once symptoms emerge. At present, no medical therapy exists that is capable of reversing or halting the progression of the illness.
Prion disorders are also unique in medicine as the only known human diseases caused entirely by infectious protein particles rather than viruses, bacteria, or parasites.
All humans carry normal prion protein in their brain tissue, which is encoded by the PRNP gene. However, when the protein's structural configuration transforms into an abnormal shape known as PrPSC, it turns into an infectious agent.
This misfolded protein binds to healthy prion proteins and converts them into the same abnormal structure. This transformation can occur due to genetic factors or cellular mechanisms that science has not yet fully identified.
Prion conditions can manifest in sporadic, familial, or acquired forms. The sporadic variation is the most common form in humans and is believed to originate from a cellular processing error where normal prion proteins spontaneously misfold. The resulting damage to the nervous system is severe and inevitably fatal.
The Role of Copper Ions in Cellular Damage
The Brazilian research team specifically investigated how copper ions influence the onset and evolution of prion conditions. The study was authored by lead researcher Mariana Juliani do Amaral of UFRJ, Yraima Cordeiro of UFRJ, and Aline Ribeiro Passos of CNPEM.
Amaral explained that copper ions concentrate within the synaptic cleft, which is the communication junction between neurons. Once concentrated in this area, the ions trigger harmful chemical reactions.
The lead author stated that these ions generate reactive oxygen species, which react with cellular biomolecules such as lipids, proteins, and DNA to cause mutations and protein aggregation.
Amaral emphasized that reactive oxygen species represent a common factor across all neurodegenerative diseases. As a result, while the investigation focused on the prion protein, its findings provide valuable insights applicable to other neurological disorders.
Advanced X-Ray Analysis and Potential Drug Targets
To observe these subtle microscopic dynamics, the team employed X-ray photon correlation spectroscopy (XPCS) on the Cateretê beamline at Sirius to track intracellular condensates.
Passos noted that conventional material characterization techniques only provide aggregate information about a whole sample rather than the detailed data required for this study.
The CNPEM co-author explained that the spatial coherence of the light beam produced by Sirius allowed researchers to analyze droplet dynamics at the micrometer scale, yielding quantitative measurements of the condensed phase and the liquid or gel states of protein droplets.
These highly concentrated protein droplets mark a significant milestone in understanding the interaction between prion proteins and copper ions.
The empirical findings support the hypothesis that these temporary liquid droplets evolve over time into highly stable protein aggregates, which subsequently trigger cellular destruction and disease progression.
Amaral commented that this discovery opens promising new opportunities for therapeutic intervention, noting that scientists previously did not know an intermediate state existed between soluble proteins and aggregated forms.
The lead author pointed out that liquid droplets could serve as viable pharmacological targets, whereas fully aggregated protein structures cannot. If medical treatments can keep the droplets in their liquid state, Amaral said it may be possible to prevent the progression of neurodegenerative diseases.
The investigation was developed in collaboration with international researchers, including Professor Susanne Wegmann of the German Center for Neurodegenerative Diseases (DZNE), who focuses on describing phase separation processes under cellular stress.
