Dorn II, Gerald W. Division of Biology and Biomedical Sciences, Washington University, St. Louis, Missouri.
- Mitochondria and mitophagy
- Parkin and PINK1
- Mitochondrial quality control
- Links to Primary Literature
- Additional Readings
PINK1 [PTEN (phosphatase and tensin homolog)–induced kinase-1] and Parkin are the prototypical protein factors for which single-gene human mutations were first linked to rare, hereditary forms of Parkinson's disease. Parkinson's disease is a multifactorial progressive neurodegenerative condition characterized by the loss of nerve cells (neurons), especially in a part of the midbrain called the substantia nigra. Because the affected nigrostriatal neurons have high levels of the neurotransmitter dopamine, Parkinson's disease has been treated traditionally with drugs, such as l-dopa or dopamine agonists, which enhance neuronal dopamine signaling. However, such treatments do not address the cause of the disease, which is neuronal death. Indeed, it was genetic studies that identified the mutations (first in Parkin and subsequently in PINK1) that ultimately revealed the mechanism for neuronal toxicity underlying the inherited forms of Parkinson's disease, specifically, a defect in the mitochondrial quality control.
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