Convergence of Parkinson’s disease and diabetes: focus on glia

Abstract

Inflammation is an important aspect of the etiology of many diseases that are prevalent in the aging population, such as Parkinson’s disease (PD) and diabetes mellitus (DM). As the aging population grows, the number of PD and DM cases is expected to rise. Therefore, a better understanding of the role of inflammation in both diseases, as well as the potential interaction between PD and DM, is paramount. Both diseases impact the central nervous system. Moreover, we and others have found evidence implicating DM as a predisposing factor in PD onset and vice versa . This relationship between the two diseases implicates common factors in their pathogenesis, an important one of which is inflammation of the CNS, i.e. neuroinflammation. Microglia are considered the resident macrophages of the CNS, and current research indicates that microglial activation promotes neuroinflammation, triggering neurodegeneration. In this review, we focus on neuroinflammation as a convergent mechanism for PD and DM pathogenesis, with microglia as the central player. It is currently unknown whether DM- or PD-associated CNS inflammation originate in the periphery or in the CNS. Therefore we consider common inflammatory and neurodegenerative features of PD and DM, including the roles of astrocytes as well as increased blood brain barrier permeability and peripheral monocyte invasion. Anti-inflammatory therapies have been tested in both DM and PD. While such therapies may be modestly effective for DM and PD, they are likely to perform better in combination with other therapeutic approaches and be used more effectively as understanding of the mechanisms of inflammation in DM and PD pathogenesis evolves. Lastly, we provide new data showing that a mouse model of Type I diabetes displays an elevation in brain glutaredoxin-1 (Grx1), an important pro-inflammatory enzyme in immune cells; and this enzyme induction is followed by diminution in dopaminergic neuronal projections indicative of PD onset.