Overzealous Microglial Cells May Be Responsible For The Neurodegeneration Seen In Alzheimer’s
For the first time in existence, scientists have been able to illustrate an effect of the scavenger cells of our brain, the microglia, which will take you by surprise. If the microglia lack a protein by the name of TDP-43, not only will these brain cells remove the notorious Alzheimer’s plaques but they will also destroy synapses.
Like most neurodegenerative diseases,
Alzheimer’s patients also exhibit a continuing deterioration of their cognitive
abilities. This is due to the progressively increasing synapse loss, the
meeting point of neurons in the brain. When it comes to Alzheimer’s, it is β-amyloid
protein fragments that rank high in our suspect list for the death of
neurons. β-amyloid peptides will cluster
together and produce those characteristic Alzheimer’s plaques.
According to a study
published in Neuron, researchers from
the University of Zurich are now able to demonstrate that malfunctioning
microglial cells are involved in the loss of synapses in not only Alzheimer’s
but also other neurodegenerative disorders. Microglia usually track the
functioning of our neurons by getting rid of surplus synapses produced in
development as well as harmful protein aggregates that could be toxic to the
brain. Before this, the role of microglia in association with neurodegeneration
has always been controversial.
Initially in the study, the researchers
tried to determine what impact certain genes that carry a risk for Alzheimer’s
have on β-amyloid peptide production. Examining the function of these
Alzheimer’s risk genes in neurons, they found no impact. This caused them to
start examining microglial cells, leading to a discovery- if they turned off
the gene responsible for TDP-43 protein production in microglia, the scavenger
cells would get rid of β-amyloid with greater efficiency. This is because a
lack of the TDP-43 protein causes an increase in the phagocytic activity, i.e.
the scavenging abilities, of the microglia.
The researcher’s then proceeded to use
mice, where once again they turned off the TDP-43 production in mice microglia.
They were able to discover that not only did the scavenger cells effectively
remove the β-amyloid, astonishingly, the boosted scavenging competencies of
microglia caused mice to lose a significant amount of synapses as well. This
has led the researchers’ to hypothesize that maybe once we age, dysfunctional scavenger
cells maybe exhibiting deviant phagocytosis.
What Does This Mean?
What the results exhibit is that the role
of microglia in regards to neurodegeneration seen in Alzheimer’s has been
profoundly underestimated. Microglia aren’t only restricted to inflammatory
processes and neurotoxic molecule release in the course of Alzheimer’s as
previously conjectured. According to the researchers, this dysfunction noted in our microglia may be a crucial reason as to why during clinical testing, Alzheimer's drugs decrease β-amyloid plaques but the patient's cognitive abilities do not improve.
1. Rosa C. Paolicelli, Ali Jawaid, Christopher M. Henstridge, Andrea Valeri, Mario Merlini, John L. Robinson, Edward B. Lee, Jamie Rose, Stanley Appel, Virginia M.-Y. Lee, John Q. Trojanowski, Tara Spires-Jones, Paul E. Schulz, Lawrence Rajendran. TDP-43 Depletion in Microglia Promotes Amyloid Clearance but Also Induces Synapse Loss. Neuron, 2017; DOI: 10.1016/j.neuron.2017.05.037
Well written and very interesting! Keep posting my friend :)
ReplyDeleteThanks Nina! I'm thinking of simply writing a condensed accounting of curated studies. Hopefully lol I keep up with this ;)
Delete