Report
Teaser, summary, work performed and final results
Periodic Reporting for period 3 - NEUROMITO (Elucidating Neuronal Susceptibility to Mitochondrial Disease)
Teaser
Mitochondria generate most of the energy cells require to function. Deficits in the mitochondrial energy-generating machinery affect 1:5,000 children and cause progressive, debilitating, and usually fatal pathologies collectively known as primary mitochondrial disease. To...
Summary
Mitochondria generate most of the energy cells require to function. Deficits in the mitochondrial energy-generating machinery affect 1:5,000 children and cause progressive, debilitating, and usually fatal pathologies collectively known as primary mitochondrial disease. To date, there is no cure for mitochondrial disease and existing treatments are highly ineffective and mostly palliative. High-energy-requiring cells, such as neurons, are especially affected in mitochondrial disease. However, not all neuronal populations are equally affected and the molecular alterations leading to this vulnerability are unknown. To improve on current knowledge on mitochondrial disease and to provide better therapeutic targets, Neuromito focuses on developing new tools that will allow to dissect the mitochondrial function with unprecedented resolution. These tools will help identifying novel therapeutic targets that will lead to effective treatments for mitochondrial disease. Neuromito is divided in three research lines: identifying and characterizing the neuronal circuits affected by mitochondrial disease, determine the molecular alterations in such neurons, and identifying molecular targets with therapeutic potential.
Work performed
To date, we have successfully identified and characterized the affected neuronal populations in a model of mitochondrial disease. Furthermore, we have already developed and validated several molecular biology tools to allow the characterization of mitochondrial function in specific cell types. Using these tools, we have been able to provide a comprehensive description of the molecular and elecrophysiological alterations in different neuronal populations in response to mitochondrial dysfunction.
Final results
Ongoing research is aimed at implementing this novel technology in a model of mitochondrial disease to uncover the molecular underpinnings causing neuronal death in this pathology, to elucidate the biological consequences of each of these neuronal populations in the development and progression of the disease and to identify molecular pathways that can provide novel therapeutical targets.
Website & more info
More info: http://www.quintanalab.org/neuromito-elucidating-neuronal-susceptibility-to-mitochondrial-disease.