Anavex Life Sciences Corp (AVXL)

[sokol]

Peroxynitrite Is a powerful oxidant that, among other things, inhibits mitochondrial respiration. Mitochondrial dysfunction is reported as a cause of Alzheimer's disease and as a factor that contributes to other CNS diseases. Mitochondrial dysfunction is a result of oxidative stress. ANAVEX 2-73 is believed to have CNS disease-modifying effects, including the ability to repair normal mitochondrial functionality.

1. Anavex 2-73 inhibits oxidative stress by inhibiting the release of intracellular calcium... Lane article. (Lane also mentions that Anavex 2-73, a tetrahydrofuran, can be an H donor, which Doc contradicts, but so far I see no other authority for this one way or another; nevertheless, inhibiting oxidative stress is key to preventing and/or relieving CNS diseases).

2. For more than half a century free radical-induced alterations at cellular and organ levels have been investigated as a probable underlying mechanism of a number of adverse health conditions. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4462847/

3. Apoptosis, an essential physiological process that is required for the normal development and maintenance of tissue homeostasis, is mediated by active intrinsic mechanisms, although extrinsic factors can also contribute. Aerobic metabolism induces the production of reactive oxygen species (ROS), which are able to induce oxidative stress that promotes cellular apoptosis. The mechanisms of ROS-induced modifications in ion transport pathways involves oxidation of sulphydryl groups located in the ion transport proteins, peroxidation of membrane phospholipids, inhibition of membrane-bound regulatory enzymes and modification of the oxidative phosphorylation and ATP levels. Alterations in the ion transport mechanisms lead to changes in a second messenger system, primary Ca2+ homeostasis. Ca2+ disregulation induces mitochondrial depolarization, which further augments the abnormal electrical activity and disturbs signal transduction, causing cell dysfunction and apoptosis. Control of ROS levels in cells is important, because cellular dysfunction triggered by ROS is a major factor contributing to the development of many diseases. Available evidences show that ROS can induce increases in cytosolic free Ca2+ concentration ([Ca2+]c) by release of the divalent cation from internal stores and impairment of Ca2+ clearance systems. In fact, [Ca2+]c increase is a constant feature of pathological states associated with oxidative stress and apoptosis. https://link.springer.com/chapter/10.1007/978-1-4020-9873-4_1

4. Amyloid-beta peptide has been shown to result in mitochondrial and endoplasmic reticulum stress, intracellular calcium dysregulation leading to oxidative stress and apoptosis (cell death). The authors point to the role of ANAVEX 2-73 in prevention of oxidative stress and apoptosis and other data suggesting modulation of Bcl-2 and reactive oxygen species. See Anti-amnesic and neuroprotective potentials of the mixed muscarinic receptor/sigma 1 ligand ANAVEX 2-73, a novel aminotetrahydrofuran derivative”, is available online at http://jop.sagepub.com/cgi/content/abstract/0269881110379286v1?papetoc. See also, https://www.anavex.com/anavex-2-73-journal-of-psychopharmacology-publishes-anti-amnesic-and-neuroprotective-data-against-amyloid-toxicity-for-first-of-a-new-class-in-alzheimers-disease/

5. Peroxynitrite: Peroxynitrite is a powerful oxidant exhibiting a wide array of tissue damaging effects, including lipid peroxidation, inactivation of enzymes and ion channels via protein oxidation and nitration, and inhibition of mitochondrial respiration (Virag et al., 2003). From: Handbook of Toxicology of Chemical Warfare Agents (Second Edition), 2015

6. Mitochondrial dysfunctions significantly contribute to the pathogenesis of Alzheimer's disease (AD). https://pubmed.ncbi.nlm.nih.gov/26971932/

Lastly,

"In a scientific study conducted in France at the University of Montpellier and INSERM, ANAVEX 2-73 demonstrated disease-modifying effects, including the ability to repair normal mitochondrial functionality in the hippocampus, the part of the brain involved with learning, memory and emotions. Mitochondrial dysfunction has been consistently reported as an early cause of Alzheimer’s disease. It appears before amyloid-beta plaques can start to accumulate and memory loss begins in Alzheimer’s patients and transgenic mice. In the same study, ANAVEX 2-73 blocked apoptosis (cell death) and oxidative stress, which is believed to prevent the onset of Alzheimer’s disease.

'ANAVEX 2-73 appears to be a valuable drug for protection against mitochondrial damages relative to Alzheimer’s disease physiopathology,” said Tangui Maurice, PhD, CNRS Research Director, Head of Team 2 ‘Endogenous Neuroprotection in Neurodegenerative Diseases’, at the University of Montpellier and INSERM. “The unique target combination of the drug is responsible for its activity on mitochondrial dysfunction which is likely the triggering event of the pathology.'

The new study data was revealed in a presentation at the international conference on Alzheimer’s and Parkinson’s Diseases in Florence, Italy. .... The presentation is titled, “Mitochondrial protection in mouse hippocampus against Aß25-35 toxicity is induced by the novel tetrahydrofuran derivative ANAVEX2-73, a mixed s1 receptor and cholinergic agonist.”

https://www.anavex.com/anavex-2-73-restores-mitochondrial-functionality-blocks-cell-death-and-oxidative-stress-preventing-onset-of-alzheimers-disease/