Fighting against Parkinson's disease with a new SGK1 inhibitor

Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons of the Substantia Nigra and the accumulation of protein aggregates, called Lewy bodies, where the most abundant protein is alpha-synuclein (a-SYN). In addition to the neurodegeneration and the accumulation of proteins, PD is characterized by chronic low-grade inflammation and mitochondrial alterations that lead to oxidative stress. Currently, the only treatment for PD patients is dopamine replacement therapy (levodopa), which has serious side effects and does not stop the degenerative condition. For this reason, we wanted to address this challenge by developing a new SGK1 kinase inhibitor to alleviate the three main hallmarks: neurodegeneration, neuroinflammation, and oxidative stress/ferroptosis, responsible of dopaminergic neuron death. We carried out a multidisciplinary approach to evaluate a new small molecule capable of selectively inhibiting SGK1. Our results suggest that this new SGK1 inhibitor is capable of alleviating the motor alterations, and preventing the neurodegenerative and neuroinflammatory processes associated with a-SYN overexpression. While further studies are warranted, our preliminary findings suggest that SGK1 inhibitor treatment could be a promising therapeutic approach for patients with PD.