New research is increasingly focusing on the role beta-amyloid protein fragments have in people who develop Alzheimer's.
The protein fragments are believed to begin destroying synapses first, then aggregate in clusters where they start to interrupt cell transmission, leading to the death of the brain cells.
The protein, however, is believed to begin its destructive action much before symptoms appears, which is something scientists had suspected, since loss of memory starts to manifest itself in particular ways long before the full blown disease appears. This study however, as we will see, puts that onset decades before what is believed to be the onset so far.
The Harvard University Scientists who participated in the study, which was done both in laboratory mice and on human brain tissue, are aware that such a discovery explains why almost every medication on the market and experimentally has so far failed to yield any results in treating or even stalling the disease.
The discovery however, is very significant in terms of future therapy. Understanding the process of bonding to the cell pathway, and finding ways to disrupt both the bonding and aggregation of the protein fragment could provide a permanent solution to the problem of Alzheimer's.
One of the way the protein fragment is able to bond with the synaptic tissue, is through another protein called PirB, which has high affinity with beta-amyloids. This process is crucial since once the bonding of the two protein occurs, the biochemical reaction that follows is what causes the destruction of the synapses.
PirB was once thought to only be present in tissue outside the brain. The discovery of its presence and function, which is to prevent the synapses from strenghtening during synaptic or brain function, thereby promoting their 'elasticity' which in turn can prevent fast shifting synaptic tension, is crucial to understanding the bonding process. Without such a brake, the brain then experiences epilepsy during certain thought processes.
The interesting find was that mice, who are by nature resistant to amyloid plaque formations, when altered genetically to possess the two genetic mutation that predispose humans to Alzheimer's, developed the disease, but did so at a very late stage. What they also found was the genetically altered mice possessed none of the strength shifting synaptic ability when still very young.
The latter discovery points to a possibility that Alzheimer's might have much earlier 'roots' than once thought, with possible onset at a very young age.
When the Harvard lead scientist, Ms. Shatz, then eliminated PirB from the genetically altered mice to see if that flexibility was restored, she noticed that the mice not only showed the synaptic flexibility of normal mice, but also the fact that they retained that flexibility even later in their lab life, even with the dual genetic modification.
In essence the mice that had been genetically modified to not have the PirB protein was protected from the amyloid plaque forming and the damage to the brain cells.
The underlying possibility is that the absence of PirB in the mice, prevented the amyloid plaque from 'hardening' or further hampering the strength flexibility of the synapses, thereby preventing the weakening and collapse of the synapses themselves.
PirB is the mice only protein that binds to amyloid protein fragments. But humans have an equally functioning counterpart. That protein is called LilrB2, and it has equally 'binding' properties for amyloid protein fragments.
The research also showed that mice that were not modified to not have PirB had an unusual amount of an enzyme called cofilin. This same enzyme is present in human sufferers of Alzheimer's at higher levels than people who do not develop the disease.
Cofilin's action in the brain is to break down actin, another protein whose action is to keep synapses healthy. When Cofilin is higher than normal, it destroys larger quantities of actin, which then results in faster destruction of the synapses.
One of the possible treatments the scientists envision if their research is confirmed fully, is to develop a medication that halts the binding of Amyloids to PirB or its human equivalent, as was possible, for example, from medications that were developed to stop viruses from adhering to Tcells.
Partial Source : ScienceDaily/ 9.20.13
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