Pten-Induced Kinase 1 (PINK1) mutations are associated with autosomal recessive parkinsonism. It is a neuroprotective kinase predominantly found in the mitochondria and cytoplasmic areas of the cell. PINK1 is also a serine/threonine protein kinase and is associated with the mitochondria. PINK1, in research studies, is generally used as a knockout (KO) model. The mechanism of action of this gene involves the recruitment of the Parkin gene from the cytoplasm to the mitochondria. Once recruited, this leads to augmented ubiquitin activity and therefore induces mitophagy. Mitophagy is a pathway in which the mitochondria is degraded. Both PINK1 and Parkin share functions in the same pathway, therefore, their activities are similar. Some studies have demonstrated expression of the PINK1 mutation in rodents, inducing dopaminergic neuron loss and motor defects. Other studies are more associated with PINK1 KO. PINK1 knockouts show reduction in dopamine levels in the striatum. They express very low levels of dopaminergic neuron loss and do not present the formation of Lewy bodies. However, the KO models demonstrate mitochondria dysfunction and oxidative stress. On the other hand, studies are demonstrating loss of dopaminergic neurons and showing motor deficits in rats.
