Mitochondrial dysfunction and disease
Mitochondrial dysfunction, which occurs when cells’ mitochondria do not work as well as they should, has emerged as a key factor in a multitude of diseases.
Dysfunctional mitochondria are the primary hallmark of many rare genetic mitochondrial disorders.
In addition, many age-related diseases including those that affect the nervous and metabolic system are associated with mitochondria dysfunction. These include Parkinson’s disease, Alzheimer’s disease and type 2 diabetes.
Idiopathic Pulmonary Fibrosis
Parkinson’s disease is a chronic, degenerative neurological disorder that affects one in 100 people over the age of 60. There is no objective test or biomarker for Parkinson’s disease, so the rate of misdiagnosis can be relatively high. As a result, estimates of the number of people living with the disease vary, although recent research indicates that at least one million people in the United States, and more than five million worldwide, suffer from Parkinson’s disease.
Proposed Mechanism of Action and Therapeutic Rationale
USP30 has been highlighted as a promising new target in the Central Nervous System (CNS) arena (Bingol et al., 2014 Nature 510: p370) based on effects on the Parkin pathway, which is mutated in certain Parkinson’s patients. Given that adult neurons do not divide, removal of dysfunctional mitochondria is essential to prevent impaired neuronal function and aid survival. Failure of mitochondrial quality control may lead to degeneration of the highly active substantia nigra neurons in the brain, a pathological mechanism that results in Parkinson’s disease. Enhancing this quality control through inhibition of USP30 could therefore be beneficial in treating Parkinson’s.