Replies to post #184489 on Anavex Life Sciences Corp (AVXL)

[georgejjl]

Elimination of ß-amyloid plaques via macroautophagy

The buildup of ß-amyloids (Aß) contribute to plaque formation in the brain, leading to Alzheimer’s disease. Protein fragments such as Aßs would theoretically be consumed by autophagosomes and then digested, but a study by Yu et al. showed that autophagy is induced in Alzheimer’s-afflicted mice, but autophagosomes unnaturally build up (2005). They hypothesize that the formation of lysosomes from these autophagic vacuoles is inhibited. To investigate the cause of this inhibition, APP/PS1 mutant mice, which exhibit Aß-buildup, should be used in the same manner of Yu et al. as a model organism. Fortunado et al. show that autolysosome fusion is impaired by a depletion in the membrane protein Lamp-2 (2009). Differences in membrane proteins in AD and control mice would be explored in addition to possible defects in their corresponding regulatory genes. Any observed reductions in proteins or differential expression of related genes could indicate a cause of impaired autophagosome-lysosome fusion.

https://www.lakeforest.edu/live/news/5512-the-importance-and-practical-application-of

Good luck and GOD bless,

[GrassyKnoll]

Two real simple answers won the S***it works. And to The fact that it works was printed inCell . It’s like reading something in the New York Times back when the New York Times was the New York Times

The emoji described in the study is probably only part of what I have a vex dies. It fixes up all Pro Tien production at the point where it’s made by sending in a fire truck to clean up a fire in the protein factory.

The proteins describe it in the paper are basically the janitor crew that cleans up after the fire. If the fire is bad the janitor can’t stand the heat or even a better analogy the machine with and makes the janitor is on fire and so there’s no janitor to show up to work

The paper shows that the janitor has returned to work and is cleaning up the mess. But in my humble opinion and has George has shown by the previous links the MOS even deeper and has to do with the fact that every pro team including the janitors proteins are made correctly

Patience is all that’s required for this one in my humble opinion

[falconer66a]

Here's the story.

...what is this CELLS article telling us "non-bio"literate folks !!!

Ok, here’s a summary of what the new paper disclosed about the efficacy of Anavex 2-73.

First, the problems the molecule corrects.

In human (and, well, murine, too) neurodegenerative diseases (such as Parkinson’s and Alzheimer’s; et al.) a major pathogenic (disease-causing) factor is the accumulation of protein wastes. In functioning cells (particularly neurons), these wastes are cleared even before they form, when they are still badly-formed or dysfunctional (worn-out) cell parts (organelles, or their like). They get eaten up, internally, by the process of “autophagy.” “Auto-” means “self,” “-phagy” means to “eat,” or “consume.” When working properly, the cell self-eats molecular structures that are failing and will soon become wastes that will disrupt normal cell chemistries.

The entire waste-clearing process is “homeostatic,” meaning “same-state;” an on-going, continuous process of maintaining the same, functioning state. Homeostasis is give-and-take. As cell parts or molecular structures wear out, give up; autophagy takes in, eats, those worn-out structures. Autophagous removal of cell-poisoning wastes keeps things in order. The “self-eating” process consumes and recycles the wastes. All is well.

But not in neurons suffering from various central nervous system diseases (including Parkinson’s and Alzheimer’s, the current Anavex 2-73 targets).

Helping to properly control autophagy are the sigma-1 receptors, when properly activated. With their activation, autophagy clears wastes effectively. Loss of sigma-1 receptor activation hinders autophagy; wastes build up, disease sets in.

Now, here’s the essence of the findings of the paper. The researchers proved that Anavex 2-73 “... a) enhances the autophagic flux in human cells and in Caenorhabditis elegans and b) increases proteostasis capacity, ultimately ameliorating paralysis caused by protein aggregation in C. elegans.” Simply stated, Anavex 2-73 restores adequate autophagy (protein waste-clearing) in poorly-functioning neurons, thereby reversing the paralysis the uncleared wastes (“protein aggregation[s]”) caused.

Very important. This was precisely and accurately observed in both human cells, HeLa cells, a widely-used, completely understood line of lab-reproducible human cells; and also in cells of Caenorhabditis elegans, a widely-studied and completely understood nematode. And, as someone else clearly posted, there is precise evolutionary conservation of the sigma-1 receptor, from worms to humans; same molecules, identical molecular structures. What is seen in the sigma-1 receptors and autophagy of C. elegans is exactly the same in humans. (With that knowledge, I wouldn’t be an AVXL short. No chance of being able to cover the shorted position with any gain.)

The paper’s authors made this claim: “Excitingly, ANAVEX2-73 is a potent inducer of autophagic flux in vitro and in vivo and ameliorates protein aggregate formation and paralysis in C. elegans.” The stuff fixes the waste-clearing dysfunction of both human and nematode cells. Without those wastes accumulating, various CNS diseases are obviated or treated.

Certainly I’m not the only person who saw all of this in the many previous Anavex 2-73 studies. There were a good number of murine studies that showed ingestion of drinking water with Anavex 2-73 successively treated lab rats with various CNS diseases. That can happen only if homeostatic autophagy can be restored. It happened back then, in those lab rats; and now, in this study, in both human cells (in vitro; growing in glass containers) and in C. elegans nematode cells (in vivo; growing in a living organism).

For me (and I’m sure, others), the findings of this paper were not particularly new. For most, the paper is perceived as valid because it was done by parties unrelated to Anavex Life Sciences Corp; “third parties.” If these same data and findings would have been published by people employed or contracted with Anavex, they would have been quickly dismissed as self-serving, contrived findings; tainted, even disqualified by a direct corporate Anavex connection.

But since Anavex played no part in this study (other than to provide requested doses of Anavex 2-73), it is, then, valid. Pretty much the same findings of a bunch of other papers (which I believed when I read those). For myself, I didn’t need this new paper to confirm the unique mechanism of action of Anavex 2-73 in poorly-functioning, waste-contaminated neurons. To me (and certainly others), it was obvious from the start.