Molecular mechanisms of degeneration and repair

Adrian Pini

Senior Lecturer

All neurodegenerative conditions whether due to trauma or otherwise are characterised by neuronal loss and glial proliferation in the same regions. How it happens that that these two classes of cells display such different responses is unknown and has fundamental clinical and scientific significance. If mediators of such phenomena can be discovered then it should be possible to take therapeutic approaches by targeting them. We are interested in the way that soluble nuclear histone proteins may contribute to neurodegeneration as we have shown that soluble histone H1 when applied to cultures of neurones and glia causes selective neuronal destruction and glial proliferation. Microglia are major components of all neuro-inflammatory conditions and histone H1 and histone H1 drives them into a pro-inflammatory state We have proposed 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.