Replies to post #176120 on Anavex Life Sciences Corp (AVXL)

[falconer66a]

Perfect Fit

Neurons naturally undergo a cellular “cleaning system” that relies on several proteins, including one called BAG3,...

Good find.

Waste tau proteins, if they accumulate in neurons, cause various symptoms of Alzheimer’s. Normal neuron physiology produces the tau protein wastes. Their production is not the problem (is quite normal). It’s their accumulation; the failure of the neuron to clear the tau wastes.

And, as this report indicates, a specific gene (not a protein, wrong info in the article), labeled BAG3, makes a protein that normally clears tau. Incomplete expression (protein generation) of this gene keeps the neuron from normally clearing the tau; tau tangles accumulate and nerve function is pathologically impaired. Alzheimer’s occurs.

How might Anavex 2-73 play a therapeutic role here? If the expression (protein generation) of this important gene is impaired, by reduced function of the endoplasmic reticulum, a result of either deficient calcium ion transport or ATP availability from the associated, connected mitochondrion, Anavex 2-73 ameliorates both of those problems. It restores normalized calcium ion transport between the endoplasmic reticula and the mitochondria, and allows full ATP production in the mitochondrion and transport to the adjacent endoplasmic reticulum, where the now-sufficient ATP energy is used to fold proteins into functional configurations.

In order for the protein produced by the BAG3 gene to function in clearing tau wastes, it must be perfectly folded. Just as a bent key won't fit into or open a lock, improperly-folded proteins cannot connect with and react with their targeted reactants (tau wastes in this case). Allowing endoplasmic reticula to properly fold proteins is a major therapeutic factor of Anavex 2-73.

Plug this into some transgenic rats with the defective gene. See if tau wastes are consequently cleared.

[Steady_T]

Thanks for bringing that to the board. An interesting read.

These articles show how much is unknown about AD and how many different avenues of research are going on at the same time trying to understand the basis of the disease.

For me, they also highlight the complexity of the interrelated systems going on in the brain and how a disturbance in one part of a specific system can have a negative effect on another system.

Medicine is hard. CNS diseases are harder.