Chaperone proteins play role in neuroprotection by fatty acids

The earlier post on Omega-3 suggests a very broad applicability and therapeutic potential for polyunsaturated fatty acids in central nervous system disease and dysfunction. It does, however, skip around the issue of how this can possibly be and the mechanism by which it may give rise to these beneficial effects. The reason for this is that we really don’t know.

An observation one can make is that all therapeutic examples – in the trauma setting at least – appear to require very acute delivery (within an hour) for efficacy to be demonstrated. What this is telling us, I’m not sure, but it is an important and intriguing observation sentinel which is surely pointing to something. Anyway, JD Figueroa [presentation 341.30] presented a poster on so-called chaperone proteins that are required to bind fatty acids such as DHA (making this fatty molecule more soluble in the watery biological environment) used in the studies referred to in an earlier post.

Figueroa and colleagues are studying something called the fatty acid-binding protein 5 (FABP5). Present in neurons in the uninjured cord, after injury the level of FABP5 appears to increase significantly during the first week in Glial cells such as astrocytes and oligodendrocytes. This story is far from complete but a key experiment they performed was to look at what happened when they blocked the production of the chaperone FABP5. Normally the administration of the fatty acid DHA led to improvements in function but blocking FABP5 resulted in poorer function. While this doesn’t itself represent a therapeutic mechanism the group suggest that chaperone proteins play an important part enabling the cell to take up and make use of the therapeutic fatty acid and may itself be a potential therapeutic target.

Elsewhere, Alexander (Sasha) Rabchevsky continued his exploration of the potential beneficial effects of the licensed drug Gabapentin for autonomic dysreflexia, muscle spasticity and as presented [341.29] ameliorating the chronic inflammatory response they propose is associated with autonomic dysreflexia.

The Lu et al., paper in the high impact journal Cell last year showed that embryonic stem cell-derived neural stem cells could survive, integrate and form synapses with host tissue and regenerate to an unprecedented degree in adult spinal cord. Lu presented [342.23] on more recent work where they took fibroblast cells from a healthy adult male, and created inducible pluripotent stem cells, or IPSCs, by genetic manipulation. Again, the poster was filled with remarkable images of regenerating axons growing both up and down the cord from the graft site. If anything “the response was more robust”, said Lu. IPSCs are a potentially important source of cells that can be harnessed for therapies. Safety concerns remain with such approaches but the ability to source and expand one’s own cells for treatment is appealing.