The most important clinical fallout of dysfunctional microglia appears to be the emergence of dementia. It is indeed speculated that microglia may hold the key to stopping the notorious Alzheimer’s disease (AD). This is because microglia seem to play a role in eliminating the amyloid plaques which are thought to contribute to the disease process. Experiments suggest that there is excessive microglial activation in AD, and these supercharged microglia destructively ‘eat up’ synapses, the all-important junctions where nerve cells communicate with each other. It is also relevant that microglial activation is particularly prominent in the hippocampus, a structure critical for memory formation. Because synaptic loss is such a key feature of AD, it is hoped that a better understanding of microglial function may lead to therapeutic tools that modulate AD microglial activation.
Microglial activation also seems to play a role in another prominent neurodegenerative disease, Parkinson’s disease (PD). It is also speculated that microglia are activated in PD as a response to environmental triggers, and the activated microglia cause neuronal damage by producing toxic substances. Because this is presumably an inflammatory process, there is the hope that a better understanding of the process will open up new therapeutic possibilities.
Another disorder in which microglia may play a pathogenetic role is frontotemporal dementia (FTD) in which chronic microglial activation has been reported. It is significant that the microglial activation is most evident in the frontal cortex as this correlates with the behavioural and speech disorders which characterise FTD. More intriguingly, the activated microglia seem to express the progranulin (PGRN) gene mutations that are known to be associated with FTD. Enough clues one might say.
The reach of microglial dysfunction however goes way beyond the big three of AD, PD, and FTD. For example, microglia are acutely activated in traumatic brain injury (TBI), and this may be responsible for the damage that results from this. Microglia also appear to be relevant in cerebrovascular disorders because microglial activation has been reported in ischaemic stroke and in haemorrhagic stroke. And the cherry on top is surely the report that microglia play a role in prion disorders. It may well turn out that neuroscientists are just opening up the microglial can of worms.
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