Expression of Lewy Body Protein Septin 4 in Postmortem Brain of Parkinson's Disease and Control Subjects

In Parkinson's disease (PD) neuronal degeneration is associated with abnormal protein aggregation in various forms including Lewy bodies (LBs). A major component of LBs is alpha-synuclein; septin 4 (SEPT4), a polymerizing GTP-binding protein that serves as scaffold for diverse molecules has been found to colocalize with alpha-synuclein in LBs. The central role of SEPT4 in the etiopathogenesis of PD has been suggested since SEPT4 also shows a physiological association with alpha-synuclein and serves as a substrate for parkin. To this end, we studied the expression of septin 4 and alpha-synuclein in postmortem human substantia nigra (SN) and amygdala from patients with PD and healthy controls. Twenty patients (14 men : 6 women, onset 63.0 +/- 11.4 years, age 77.3 +/- 7.6 years, Hoehn and Yahr 4.05/5) and 9 neurologically healthy controls (4 men/5 women, age at death 80.1 +/- 8.6 years) were studied. Sporadic PD cases showed a statistically significant decrease of the fold change (FC) of SNCA (FC = 0.31, P = 0.00001) and SEPT4 (FC = 0.67, P = 0.054) gene expressions in the SN and the amygdala (SNCA: FC = 0.49, P = 0.02; SEPT4: FC = 0.32, P = 0.007) versus healthy controls. However, an increase of both proteins in PD versus control subjects was observed with immunoblotting. The semi-quantitative protein ratio calculations revealed more than 10-fold increases for both SEPT4 and alpha-synuclein in PD versus control subjects. We present for the first time similar signal expression patterns and parallel accumulation of SEPT4 and alpha-synuclein in well-characterized postmortem PD brain. Considering the heterogeneous etiology of sporadic PD and the variability of individual human samples, SEPT4 accumulation may be regarded as one of the common pathological changes in PD and should therefore be further explored.