The brain is a remarkable but fragile organ with limited ability for self-renewal following injury; it also has a very high metabolism, using approximately 20% of all energy consumed by the body and producing significant waste. Consequently, it has evolved a complex system of barriers to control the entry and exit of materials and maintain its delicate healthy balance. The CureAlz Brain Entry & Exit Consortium is investigating how each component of the brain’s entry and exit structures, along with the cerebrospinal fluid that flows through the brain, must function together to maintain health. Restoration of a single disrupted pathway may be sufficient to rescue detrimental aspects of numerous routes, offering an attractive therapeutic intervention to prevent widespread impairment.
The consortium’s members bring cutting-edge expertise to the study of these interconnected structures. They are examining how the blood-brain barrier must be selective, rather than simply exclusive, and how clearance of debris through the meningeal lymphatics system is vital to immune communication between the brain and periphery. They also are assessing how cerebrospinal fluid flow dynamics affect both exit and entry, and how it may be altered in AD as amyloid beta pathology builds up. The only drug currently FDA approved for its impact on AD pathology is delivered from the blood across the blood-brain barrier; it then tags amyloid beta for clearance from the brain. The work of the Brain Entry & Exit Consortium offers a powerful opportunity to identify new therapeutic possibilities and improve those already in development.
BRAIN ENTRY & EXIT CONSORTIUM: FUNDED RESEARCHERS
Helene Benveniste, M.D., Ph.D., Yale University School of Medicine
Se Hoon Choi, Ph.D., Massachusetts General Hospital
Richard Daneman, Ph.D., University of California, San Diego
Ali Ertürk, Ph.D., Helmholtz Munich
Fanny Herisson, M.D., Ph.D., Massachusetts General Hospital
Roger Kamm, Ph.D., Massachusetts Institute of Technology
*Jony Kipnis, Ph.D., Washington University School of Medicine in St. Louis
Fernanda Marques, Ph.D., Minho University School of Medicine
Laura Santambrogio, M.D., Ph.D., Weill Cornell Medicine
Allen Tannenbaum, Ph.D., Stony Brook University