Anavex Life Sciences Corp (AVXL)

[F1ash]

Enlightening article! Thanks for posting. It lead me to the following article which certainly helped me to understand in more simplistic terms what A2-73 hopes to address.

“Mitochondrion – much more than an energy converter

Quick look:

Mitochondrion (plur: mitochondria) – energy converter, determinator, generator (of reactive oxygen chemicals), enhancer, provider of genetic history and, controversially, an aid to boost the success rate in infertility treatment.
Mitochondria are organelles that are virtually cells within a cell. They probably originated billions of years ago when a bacterial cell was engulfed when visiting what was to become a host cell. The bacterial cell was not digested and stayed on in symbiotic relationship.
A true story of a visitor that stayed on and on……for ever. Like many visitors the guest bacterium contributes something towards its keep; the mitochondrion has certainly made sure its presence is felt. In addition to the features mentioned below mitochondria also take part in reactions concerning fatty acid metabolism, the urea cycle and the biosynthesis of the haem part of haemoglobin

Click here to view an image of mitochondria interpreted using the Gridpoint cross-hairs device

Mitochondria: the energy converters
Mitochondria, using oxygen available within the cell convert chemical energy from food in the cell to energy in a form usable to the host cell. The process is called oxidative phosphorylation and it happens inside mitochondria. In the matrix of mitochondria the reactions known as the citric acid or Krebs cycle produce a chemical called NADH. NADH is then used by enzymes embedded in the mitochondrial inner membrane to generate adenosine triphosphate (ATP). In ATP the energy is stored in the form of chemical bonds. These bonds can be opened and the energy redeemed.”

“Mitochondria: determinators
Recent research indicates that in addition to converting energy mitochondria play quite a large part in determining when a cell will die by ordinary cell death (necrosis) or programmed cell death (apoptosis). In apoptosis the mitochondrion releases a chemical, cytochrome c, and this can trigger programmed cell death (apoptosis).

https://bscb.org/learning-resources/softcell-e-learning/mitochondrion-much-more-than-an-energy-converter/

Highly recommend reading the above link in it entirety and as it helped me understand the following as it relates to A2-73 research.

“Among its conclusions, the report reveals that ANAVEX 2-73 prevents mitochondrial dysfunction and blocks resulting oxidative stress and apoptosis (cell death) in a nontransgenic mouse model of Alzheimer's disease (AD). Mitochondrial damages have been consistently reported as an early cause of AD and appear before amyloid-beta plaques and memory decline in Alzheimer's patients and transgenic mice. Thus, by preserving mitochondrial functionality and reducing other key AD hallmarks, ANAVEX 2-73 has the potential to prevent, stop, slow or reverse the disease, in addition to treating its symptoms.”

https://www.google.com/amp/s/www.cnbc.com/amp/2015/02/25/globe-newswire-anavex-2-73-could-prevent-alzheimers-disease-in-addition-to-modifying-and-treating-symptoms.html

At least validation of the sigma1 approach if not A2-73 in particular.

“We therefore evaluated the effect of ANAVEX2-73 and PRE-084, a reference s1R agonist, on preservation of mitochondrial integrity in Aß25-35-injected mice. In isolated mitochondria from hippocampus preparations of Aß25-35 injected animals, we measured respiration rates, complex activities, lipid peroxidation, Bax/Bcl-2 ratios and cytochrome c release into the cytosol. Five days after Aß25-35 injection, mitochondrial respiration in mouse hippocampus was altered. ANAVEX2-73 (0.01-1 mg/kg IP) restored normal respiration and PRE-084 (0.5-1 mg/kg IP) increased respiration rates. Both compounds prevented Aß25-35-induced increases in lipid peroxidation levels, Bax/Bcl-2 ratio and cytochrome c release into the cytosol, all indicators of increased toxicity. ANAVEX2-73 and PRE-084 efficiently prevented the mitochondrial respiratory dysfunction and resulting oxidative stress and apoptosis. The s1R, targeted selectively or non-selectively, therefore appears as a valuable target for protection against mitochondrial damages in AD.”

https://www.ncbi.nlm.nih.gov/m/pubmed/25653589/

On a tangential note.

If mitochondria are evolved from bacterium, then perhaps our systemic use of broad spectrum antibiotics is playing a role in Alzheimer’s. Just a thought.

(Bolding mine)