Endocrine Abstracts

The main pathological finding in Parkinson’s disease (PD) is the loss of dopaminergic cells in the substantia nigra (SNc). Current dopamine-replacement therapies alleviate symptoms but do not prevent disease progression. The pathophysiology of PD is unknown, but oxidative stress and neuroinflammation have been implicated. A better understanding of the cause of dopaminergic cell death may lead to the discovery of new therapies that can slow disease progression.

Annexin A1 (ANXA1), a 37 kDa protein, is implicated in PD by its presence in glial scars of Parkinsonian SNc. It has been shown to reduce inflammation and induce apoptosis in a number of inflammatory cell lines. Thus ANXA1 might play a neuroprotective role in PD by acting as an anti-inflammatory mediator in the SNc.

This study used PC12 cells differentiated with nerve growth factor (NGF) to model dopaminergic cells in order to investigate the direct effect of ANXA1 and a known neurotoxin, 6-hydroxydopamine, on their apoptosis. Using FACS-analysis the results established that PC12 cells do not express ANXA1. Hoechst-H33342 staining and the APOPercentage-assay showed for the first time that exogenous ANXA1 induced apoptosis of PC12 cells pre-treated with NGF for 24 h and 7 days. This study also showed that 6-hydroxydopamine induced apoptosis of PC12 cells, but contrastingly, 24 h pre-treatment with NGF protected against its toxicity. The data indicate that ANXA1 is acting as a cell death signal. As this appears to be a mechanism whereby ANXA1 promotes phagocytosis, at least in the periphery (Solito E et al., 2003, FASEB J 17 1544–1546), the results support the view that in vivo ANXA1 could promote phagocytotic clearance of damaged dopaminergic cells, thereby limiting the resultant neuroinflammatory-response and slowing PD progression.