Altered Expression of Growth Associated Protein-43 and Rho Kinase in Human Patients with Parkinson's Disease

Abstract

Causative treatment strategies for Parkinson's disease (PD) will have to address multiple underlying pathomechanisms to attenuate neurodegeneration. Additionally, the intrinsic regenerative capacity of the central nervous system is also an important factor contributing to restoration. Extracellular cues can limit sprouting and regrowth of adult neurons, but even aged neurons have a low intrinsic regeneration capacity. Whether this capacity has been lost or if growth inhibitory cues are increased during PD progression has not been resolved yet. In this study, we assessed the regenerative potential in the nigrostriatal system in post-mortem brain sections of PD patients compared to age-matched and young controls. Investigation of the expression pattern of the regeneration-associated protein GAP-43 suggested a lower regenerative capacity in nigral dopaminergic neurons of PD patients. Furthermore, the increase in protein expression of the growth-inhibitory protein ROCK2 in astrocytes and a similar trend in microglia, suggests an important role for ROCK2 in glial PD pathology, which is initiated already in normal aging. Considering the role of astro- and microglia in PD pathogenesis as well as beneficial effects of ROCK inhibition on neuronal survival and regeneration in neurodegenerative disease models, our data strengthens the importance of the ROCK pathway as a therapeutic target in PD.