Credit: Larissa BrownA groundbreaking study provides an unique Alzheimers treatment method focusing on memory remediation through the repair of harmed synapses, leveraging the vital role of the KIBRA protein. Research has actually revealed that KIBRA is needed for synapses to form memories, and Tracys group has found that brains with Alzheimers disease are deficient in KIBRA.The Role of KIBRA in Memory Restoration” We questioned how the lower levels of KIBRA impacted signaling at the synapse, and whether comprehending that mechanism much better could yield some insight into how to fix the synapses harmed throughout the course of Alzheimers disease,” said Buck Staff Scientist Grant Kauwe, PhD, co-first author of the research study. The team is exploring this phenomenon further, in hopes that KIBRA might be utilized as a biomarker of synaptic dysfunction and cognitive decline that might be beneficial for diagnosis, treatment planning, and tracking illness progression and reaction to therapy.Promising Results from KIBRA ResearchTo figure out how KIBRA impacts synapses, the group created a shortened practical variation of the KIBRA protein. “Our work supports the possibility that KIBRA might be utilized as a treatment to enhance memory after the start of memory loss, even though the toxic protein that caused the damage remains.
Kauwe, Pareja-Navarro et al. recognize a KIBRA-dependent mechanism to fix the plasticity at synapses that is dysregulated in neurons underlying the loss of memory in tauopathy. The art depicts the healing of the functional plasticity at synapses on neurons despite tau-induced toxicity in the brain. Credit: Larissa BrownA groundbreaking research study provides a novel Alzheimers treatment method focusing on memory restoration through the repair work of harmed synapses, leveraging the critical role of the KIBRA protein. This approach shows promise in reversing memory loss without straight attending to the accumulation of poisonous proteins.While newly approved drugs for Alzheimers show some pledge for slowing the memory-robbing illness, the existing treatments fall far brief of being effective at gaining back memory. What is required are more treatment options targeted to restore memory, said Buck Assistant Professor Tara Tracy, PhD, the senior author of a research study that proposes an alternate method for reversing the memory issues that accompany Alzheimers illness and associated dementias.Exploring New Avenues for Alzheimers TreatmentSince most present research study on possible treatments for Alzheimers concentrates on decreasing the harmful proteins, such as tau and amyloid beta, that collect in the brain as the disease advances, the group diverted away from this route to explore an option. “Rather than attempting to reduce toxic proteins in the brain, we are trying to reverse the damage triggered by Alzheimers disease to bring back memory,” said Tracy. The findings appear in the February 1 concern of The Journal of Clinical Investigation.The work hinges on a protein called KIBRA, named since it is found in the kidney and the brain. In the brain, it is primarily localized at the synapses, which are the connections in between nerve cells that allow memories to be formed and remembered. Research study has shown that KIBRA is needed for synapses to form memories, and Tracys group has actually discovered that brains with Alzheimers illness are lacking in KIBRA.The Role of KIBRA in Memory Restoration” We wondered how the lower levels of KIBRA affected signaling at the synapse, and whether understanding that mechanism better might yield some insight into how to fix the synapses harmed during the course of Alzheimers illness,” stated Buck Staff Scientist Grant Kauwe, PhD, co-first author of the research study. “What we identified is a system that could be targeted to repair synaptic function, and we are now attempting to establish a therapy based on this work.” The group initially measured the levels of KIBRA in the cerebrospinal fluid of humans. They found that higher levels of KIBRA in the cerebrospinal fluid, however lower levels in the brain, represented the intensity of dementia.” We likewise discovered this amazing connection in between increased tau levels and increased KIBRA levels in the cerebrospinal fluid,” stated Tracy. “It was really unexpected how strong the relationship was, which actually points to the function of KIBRA being impacted by tau in the brain.” The team is exploring this phenomenon even more, in hopes that KIBRA could be used as a biomarker of synaptic dysfunction and cognitive decline that could be beneficial for diagnosis, treatment planning, and tracking illness progression and action to therapy.Promising Results from KIBRA ResearchTo determine how KIBRA impacts synapses, the group produced a shortened practical version of the KIBRA protein. In lab mice that have a condition imitating human Alzheimers illness, they found that this protein can reverse the memory disability connected with this type of dementia. They found that KIBRA rescues mechanisms that promote the strength of synapses.” Interestingly, KIBRA restored synaptic function and memory in mice, in spite of not fixing the problem of poisonous tau protein build-up,” stated Kristeen Pareja-Navarro, co-first author of the research study. “Our work supports the possibility that KIBRA might be utilized as a treatment to enhance memory after the start of memory loss, even though the toxic protein that caused the damage stays.” Along with other treatments that already exist or will come in the future, a KIBRA treatment to fix synapses could be a valuable addition. “Reducing poisonous proteins is naturally crucial, however fixing synapses and improving their function is another crucial factor that might assist,” said Tracy. “Thats how I see this making the biggest impact in the future.” Reference: “KIBRA repairs synaptic plasticity and promotes resilience to tauopathy-related memory loss” by Grant Kauwe, Kristeen A. Pareja-Navarro, Lei Yao, Jackson H. Chen, Ivy Wong, Rowan Saloner, Helen Cifuentes, Alissa L. Nana, Samah Shah, Yaqiao Li, David Le, Salvatore Spina, Lea T. Grinberg, William W. Seeley, Joel H. Kramer, Todd C. Sacktor, Birgit Schilling, Li Gan, Kaitlin B. Casaletto and Tara E. Tracy, 1 February 2024, The Journal of Clinical Investigation.DOI: 10.1172/ JCI169064Other Buck researchers associated with the research study are: Lei Yao, Jackson H. Chen, Ivy Wong, Helen Cifuentes, Samah Shah, and Birgit Schilling
