Pathological mechanisms and treatment of sporadic Parkinson's disease: past, present, and future.

For a special issue, we review studies on the pathogenesis of nigral cell death and the treatment of sporadic Parkinson's disease (sPD) over the past few decades, with a focus on the studies performed by Prof. Mizuno and our group. Prof. Mizuno proposed the initial concept that mitochondrial function may be impaired in sPD. When working at Jichi Medical School, he found a decrease in complex I of the mitochondrial electron transfer complex in the substantia nigra of patients with Parkinson's disease (PD) and MPTP models. After moving to Juntendo University as a professor and chairman, he continued to study the mechanisms of cell death in the substantia nigra of patients with sPD. Under his supervision, I studied the relationships between PD and apoptosis, PD and iron involvement, mitochondrial dysfunction and apoptosis, and PD and neuroinflammation. Moving to Kitasato University, we focused on PD and the cytotoxicity of alpha synuclein (αSyn) as well as brain neuropathology. Eventually, I moved to Osaka University, where I continued working on PD and αSyn projects to promote therapeutic research. In this paper, we present the details of these studies in the following order: past, present, and future.