Role of Heat Shock Protein 27 (HSP27) in the Pathogenesis of Neurodegenerative Diseases

Introduction: Many neurodegenerative diseases are characterized by neuronal inclusion bodies that share common co-localizing proteins, including chaperone proteins like heat shock protein 27 (HSP27). Although HSP27 has been extensively investigated in vivo or in vitro with regard to normal protein homeostasis, its role in the pathogenesis of Frontotemporal Lobar degeneration (FTLD) or Motor Neurone Disease (MND) is unclear. Objective and Methods: The aim of this study is to determine the role of HSP27 in the pathogenesis of FTLD and MND by comparing the amount and distribution of HSP27 immunostaining in patients with FTLD and MND with normal controls and others with Alzheimer’s Disease (AD). Semi-quantitative rating of HSP27 staining was analysed by Pearson Chi-Square Test and non-parametric Kruskal-Wallis test with post hoc Mann-Whitney test, respectively. Result: There were distinct patterns of HSP27 expression in FTLD and MND with respect to different types of neurons or glial cells. In patients with FTLD and AD, numerous intensely immunostained HSP27-positive granules were observed in the cytoplasm of pyramidal neurons of the frontal and temporal cortex, along with diffuse clusters of granules within glial cells. In the hippocampus, these changes were particularly severe in CA regions, and in cells of the dentate gyrus. Similar, though less intense, changes were seen in these same brain areas in patients with MND and in control subjects. Generally, a greater proportion of patients with AD and FTLD were severely affected than in MND and controls. Conclusion: The expression patterns of HSP27 in these neurodegenerative diseases reflect the different degrees of ongoing neurodegeneration in these brain areas, and may evidence a misfolding of damaged or unwanted proteins leading to failures in protein degradation.