A new study conducted at The Scripps Research Institute has revealed insights into the mechanism behind mitochondrial dysfunction, a key factor in the development of neurodegenerative diseases such as Alzheimer’s. The researchers analyzed neuron models derived from individuals with and without a genetic mutation causing Alzheimer’s disease and found disruptions in the Krebs cycle, a vital process for energy production in mitochondria. This discovery provides valuable information for the development of potential drug targets aimed at restoring energy production and improving signaling in the synapses.
Mitochondria, the powerhouses of cells, play a crucial role in energy production. Any disruption in their function can have detrimental effects on cell signaling and overall cognitive function. In the case of Alzheimer’s disease, abnormalities in mitochondrial activity and signaling have been observed in the neurons of mouse models before the onset of the disease. This suggests that targeting mitochondrial dysfunction could be a potential avenue for therapeutic intervention.
The researchers at The Scripps Research Institute focused on understanding the specific mechanisms underlying mitochondrial dysfunction in Alzheimer’s disease. By analyzing neuron models from individuals with and without the genetic mutation associated with the disease, they identified disruptions in the Krebs cycle. This cycle is responsible for generating energy in mitochondria through the breakdown of glucose and other molecules.
The study found that restoring energy production using a succinate analog, a compound that mimics the function of succinate in the Krebs cycle, improved signaling in the synapses. This suggests that targeting the Krebs cycle and restoring energy production could potentially alleviate the cognitive problems associated with Alzheimer’s disease.
The research team is now working on developing a drug target that can address the disruptions in the Krebs cycle and restore energy production in mitochondria. This could pave the way for future therapeutic interventions that target mitochondrial dysfunction in neurodegenerative diseases.
In addition to investigating mitochondrial dysfunction, the researchers are also exploring other factors contributing to nerve cell damage in Alzheimer’s disease using human neuron models. This includes studying inflammatory pathways and their role in the development and progression of the disease. By gaining a deeper understanding of the underlying mechanisms, researchers hope to develop more effective treatments for neurodegenerative diseases like Alzheimer’s.