Expression of Lewy body protein septin 4 in postmortem brain of Parkinson's disease and control subjects

Lina Shehadeh, Georgia Mitsi, Nikhil Adi, Nanette Bishopric, Spyridon Papapetropoulos

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

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 α-synuclein; septin 4 (SEPT4), a polymerizing GTP-binding protein that serves as scaffold for diverse molecules has been found to colocalize with α-synuclein in LBs. The central role of SEPT4 in the etiopathogenesis of PD has been suggested since SEPT4 also shows a physiological association with α-synuclein and serves as a substrate for parkin. To this end, we studied the expression of septin 4 and α-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 α-synuclein in PD versus control subjects. We present for the first time similar signal expression patterns and parallel accumulation of SEPT4 and α-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.

Original languageEnglish (US)
Pages (from-to)204-210
Number of pages7
JournalMovement Disorders
Volume24
Issue number2
DOIs
StatePublished - Jan 30 2009

Keywords

  • Alpha-synuclein
  • Amygdala
  • Gene expression
  • mRNA
  • Parkinson's disease
  • Postmorten brain
  • Protein
  • Septin 4
  • Substantia nigra

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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