HSP25 and HSP25-P-Ser15 Prompt Innate Neuroprotection in Lobe X of the Cerebellum

The cerebellar cortex presents a repetitive structure, but the main projecting neurons of this tissue, the Purkinje cells, are not identical and behave differently to various types of injury. Common patterns of neurodegeneration exist, where certain Purkinje cells die earlier than others. By contrast, lobe X of the cerebellum is a particularly resistant structure, independently of the cerebellar disease or damage. However, the mechanisms underlying the survival capability of these especially resistant Purkinje cells are still unknown. In this work, we have used the Purkinje Cell Degeneration (PCD) mouse, a model of severe cerebellar degeneration that also reproduces the human disease called childhood-onset neurodegeneration with cerebellar atrophy, to study Purkinje cell resistance. After an exhaustive immunochemical analysis of the different subpopulations of Purkinje cells, the Heat Shock Protein 25 (HSP25) and its phosphorylated version HSP25-P-Ser15 were found to be especially induced in lobe X of PCD mice. As this protein has neuroprotective properties, it may be responsible for resistance against cerebellar neurodegeneration. Taking into account the constant resistance of lobe X, the use of HSP25 may lead to new possibilities for achieving natural protection both in cerebellum and in other brain structures, or even for developing future neuroprotective therapies.