Considering Histone H1 in Age-Related Neurodegeneration
Like all tissues, the brain and nervous system become damaged and dysfunctional with age. While the underlying root causes, the differences between old tissue and young tissue, are well cataloged, how this process unfolds to create specific age-related diseases is still a matter for debate and investigation. If you care about rejuvenation and repair, you don't need to know much more than we do today in order to work on treatments to reverse the differences, but most researchers aim at greater understanding of the process, rather than actually doing something about it. Here researchers look at a small slice of the process of aging and damage in one type of tissue:
In neurodegenerative conditions and following brain trauma it is not understood why neurons die while astrocytes and microglia survive and adopt pro-inflammatory phenotypes. We show here that the damaged adult brain releases diffusible factors that can kill cortical neurons and we have identified histone H1 as a major extracellular candidate that causes neurotoxicity and activation of the innate immune system. Extracellular core histones H2A, H2B, H3 and H4 were not neurotoxic.Innate immunity in the central nervous system is mediated through microglial cells and we show here for the first time that histone H1 promotes their survival, up-regulates MHC class II antigen expression and is a powerful microglial chemoattractant. We propose that when the central nervous system is degenerating, histone H1 drives a positive feedback loop that drives further degeneration and activation of immune defences which can themselves be damaging. We suggest that histone H1 acts as an antimicrobial peptide and kills neurons through mitochondrial damage and apoptosis.