Anavex Life Sciences Corp (AVXL)

[XenaLives]

Compiled: MOA and MEDICAL SCIENCE DISCUSSION 09/29/19
____________________________________________________________________________________

Will Anavex Treat Multiple CNS Diseases?
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=150996290
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=150996631
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151220456

Endoplasmic reticulum-mitochondria crosstalk: from junction to function across neurological disorders.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=150934998

Anavex mention in paper (from georgejjl)
"Metformin and simvastatin have also been shown, experimentally, to promote autophagy, both supposedly via the activation of AMPK, and are used for the treatment of diabetes and obesity, respectively [55]. Sig-1R agonists are under intense investigation for the treatment of different neurodegenerative diseases, including AD and ALS [15,56,57]. It is actually the combination of receptor activities that may make ANAVEX2-73 an interesting compound for AD therapy [58] and, indeed, this compound is currently in active clinical studies in both neurodevelopmental (Rett syndrome) as well as neurodegenerative diseases (AD, PD)."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468724/

Exosome:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151287414
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151288272

Schwann Cells:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151277990
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151283100&txt2find=schwann
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151284243&txt2find=schwann

Some FYI from the 5/19 10-Q regarding the science.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=148704240

From kevli33 - a blast from the past:
Jan 2018 Webcast of " Central Nervous System: Is there a cure for Alzheimer’s on the Horizon? "
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146009833

History and progress of hypotheses and clinical trials for Alzheimer’s disease pub. 8/23/19 (from Greenspam3)
https://www.nature.com/articles/s41392-019-0063-8
Comments on above:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=150735844
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=150738103
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=150738889
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=150739265

Fire station analogy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=144927755

Anavex MOA described -
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145657588

A nice blog giving an overview of neurotransmitters:
https://poweronpoweroff.com/blogs/longform/a-guide-to-neurotransmitter-balance

Hampel's August 2018 statement on the action of 2-73:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145787370

The Unique Anavex Mechanism of Action and why it works differently than Donepezil
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145634041
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145648700
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146528112

Drug binding and efficacy are not the same :
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=138603679

________________________________________________________________________________________________
Sigma-1:

A2-73 mixed S1R and Muscarinic modulation - not just S1R. (from Investor2014)
Citation from this paper: https://www.google.co.uk/amp/s/www.researchgate.net/publication/11175896_AF150S_and_AF267B_-_M1_muscarinic_agonists_as_innovative_therapies_for_Alzheimer's_disease/amp

The Sigma-1 Receptor in Cellular Stress Signaling (from kevli33)
https://www.frontiersin.org/articles/10.3389/fnins.2019.00733/full

The sigma-1 receptor enhances brain plasticity and functional recovery after experimental stroke (from georgejjl)
https://academic.oup.com/brain/article/134/3/732/445636

Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo
Published: 2 March 2019 - free full text access now available (from nidan7500 )
https://www.mdpi.com/2073-4409/8/3/211/htm

Dr. James E. Barrett Ph.d., from Drexel Univ. at the Univ. of New England - UNECOM Biomedical Research Seminar
Sigma-1 Chaperones for the Treatment of Pain, Neurodegenerative Disorders and substance Abuse
Pre 084 is among those looked at.

From tradeherpete, comments on the above:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=149667334

BDNF, Sigma-1, and Huntington Disease
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=149255300

Several recent publicatons:(from Nidan7500)
https://www.frontiersin.org/research-topics/8795/sigma-1-receptor-neuronal-functions-disorders-of-the-nervous-system-and-therapeutic-potential#articles

Sig-1R is an integral endoplasmic reticulum (ER) membrane protein which forms an oligomer and binds a variety of psychotropic drugs.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=150365993

Endoplasmic reticulum proteostasis impairment in aging:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=150881937

PubMed index of info on sigma-1 receptor from kevli33:
https://www.ncbi.nlm.nih.gov/pubmed/?term=sigma-1+receptor

Sig-1R and exosomes:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=14293179

Deep dive into history of Sigma-1 Receptor - the start of a good discussion by several posters, do read forward from here:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=149338341
Comments on the above:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=149339271
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=149339973

The Roles of Intracellular Chaperone Proteins, Sigma Receptors, in Parkinson's Disease (PD) and Major Depressive Disorder (MDD).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537631/

Anti-amnesic and neuroprotective potentials of the mixed muscarinic receptor/sigma1 (s1) ligand ANAVEX2-73, a novel aminotetrahydrofuran derivative (from georgejjl)
https://www.researchgate.net/publication/46191396_Anti-amnesic_and_neuroprotective_potentials_of_the_mixed_muscarinic_receptorsigma1_s1_ligand_ANAVEX2-73_a_novel_aminotetrahydrofuran_derivative

What the Sigma-1 receptor does:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145690421

What the Sigma-1 receptor is:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145774636
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147249382

Sigma-1 Receptor as a Pluripotent Modulator in the Living System
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147249865

Broad application of the Sigma-1 (from georgejjl)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158303/

Roles of sigma-1 receptors on mitochondrial functions relevant to neurodegenerative diseases.
(2017 article from mapman1010)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603014/pdf/12929_2017_Article_380.pdf

Article 4/23/19
Sigma-1 Agonists Offer Combination Approach to Dementia Symptoms
Research from the past decade suggests that sigma-1 receptors and their encoding gene, SIGMAR1, together act as a therapeutic target for patients with dementia.
Published: April 23, 2019 Contributed by Mikesc
https://www.neurologylive.com/journals/neurologylive/2019/april-2019/sigma1-agonists-offer-combination-approach-to-dementia-symptoms

What may set AVXL 2-73 apart from other S1 receptor agonists.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145782971

November 2018 publication on Sigma-1 - note the dates of publication history starting in 2016:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771390/pdf/CN-16-97.pdf

Dr. Tangui Maurice on the Sigma-1 - 2015 video:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=143980208

History of the Sigma-1 Receptor:
molpharm.aspetjournals.org/content/89/1/142

Sigma-1 in Cancer
https://www.ncbi.nlm.nih.gov/pubmed/23988449
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274865/

Myristic acid hitchhiking on sigma-1 receptor to fend off neurodegeneration (fom georgejjl)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827442/

SIGMA-1 RECEPTOR AGONISM: THE NOVEL TREATMENT OPTION IN RENAL DISEASE. Ádám Hosszú
https://docplayer.net/96707227-Sigma-1-receptor-agonism-the-novel-treatment-option-in-renal-disease-adam-hosszu.html

How the Sigma-1 affects every cell in the body:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146258203
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MUSCARINIC RECEPTORS:


M1 Muscarinic Receptor Activation Rescues ß-Amyloid-Induced Cognitive Impairment through AMPA Receptor GluA1 Subunit. (from georgejjl)
https://www.ncbi.nlm.nih.gov/pubmed/30981860

M1 Muscarinic Receptors Modulate Fear-Related Inputs to the Prefrontal Cortex:(from georgejjl)
https://www.ncbi.nlm.nih.govThi/pubmed/31003787

The M1 muscarinic acetylcholine receptor subtype is important for retinal neuron survival
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=148297709
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PROTEOSTASIS and CELLULAR HOMEOSTASIS:

What is proteostasis?
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147258047

"Proteostasis involves the checkup of cellular proteome stability and functionality by heat-shock chaperones and degradation pathways in charge of maintaining the cells free from toxic proteins.
From: Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, 2017
https://www.sciencedirect.com/topics/medicine-and-dentistry/protein-homeostasis

Sokol gives us scientific studies to support 2-73 restoration of cellular homeostasis:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145694010

The protein folding problem: a major conundrum of science: Ken Dillposted by georgejjl

More on protein folding:
https://physicsworld.com/a/quantum-approach-reveals-faster-protein-folding/

A Delicate Balance: Fluoroquinolones Disrupt Cellular Homeostasis
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=150872773

Endoplasmic reticulum-mitochondria crosstalk: from junction to function across neurological disorders.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=150934998

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AUTOPHAGY:

This MOA applies to the aging process in general:

What is autophagy? (from nidan7500) video from Investor 2014.
https://www.news-medical.net/health/What-is-Autophagy.aspx

What is autophagy (from Pennydouble):

https://www.news-medical.net/life-sciences/What-is-Autophagy.aspx

Recent Comments (09/28/19)
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=150996290
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=150996631

Exosomes and Autophagy: Coordinated Mechanisms for the Maintenance of Cellular Fitness
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151304316

Anavex 2-73 As A Psychotropic Drug?
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151327577

NEWS!!! March 4, 2019 Third party paper on cellular recycling.
https://www.anavex.com/anavex-life-sciences-reports-publication-of-new-data-that-show-anavex2-73-induces-cellular-recycling-process-linked-to-the-prevention-and-treatment-of-age-associated-diseases/

Access to above paper
https://www.mdpi.com/2073-4409/8/3/211/htm

Summaries of the autophagy paper:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147424647
https://parkinsonsnewstoday.com/2019/03/07/study-reveals-neuroprotective-mechanisms-anavex-2-73/

On autophagy and ageing.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=150048309

Eventually, It Will Be Anavex Prophylaxis
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=148461516
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=148463672
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147257995
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147361303

Modulation of autophagy by BDNF underlies Synaptic Plasticity
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147538457

Now we have the Firetruck and Garbagetruck (from Investor2014):
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147358699

Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147423046

A series of posts on autophgy from georgejjl
#184496 Autophagy and mitophagy in ALS.
#184495 New preclinical data establishes ANAVEX®2-73 as a modulator
#184494 Role of autophagy in the pathogenesis of multiple sclerosis
#184493 Dysregulation of autophagy and mitochondrial function in Parkinson’s disease
#184492 Impairment of the macroautophagy: a possible hallmark of
#184491 Elimination of ß-amyloid plaques via macroautophagy
#184490 Protein Misfolding and Accumulation as Root Cause in Neurodegeneration
First post in series: https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147417660

There are no posts mentioning autophagy on this board prior to 2015.

2015 posts mentioning autophagy - one each from georgejjl and TrueTrades:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=118317394&txt2find=autophagy
Link to the entire paper referenced by TrueTrades:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807076/pdf/mol.113.087809.pdf

2016 posts mentioning autophagy - three from georgejjl:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=121979414&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=122985309&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=126356651&txt2find=autophagy

Potential Roles of Mitochondria-Associated ER Membranes (MAMs) in Traumatic Brain Injury (from george jjl in 2017)
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=129858549

Autophagy not mentioned again until two posts on 3/9/18 by mapman1010.
It's interesting that it was almost precisely one year before the current paper:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=139184780&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=139185523&txt2find=autophagy

Discussion of the above:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=140322574&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=140431749&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=140576574&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=140709556&txt2find=autophagy

Autophagy other 2018 mentions:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=141039429&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=141231591&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=141689338&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=141909594&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=141925525&txt2find=autophagy

ER–mitochondria signaling in Parkinson’s disease (from mapman's link to article post below)
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=142355746&txt2find=autophagy
PDF of the article cited:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832754/pdf/41419_2017_Article_79.pdf

Autophagy and late Alzheimer's:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=143131392&txt2find=autophagy

Amateur17 linked to this article on research done in Australia in 2018:
Alzheimer's tied to brain's 'waste removal system'
https://www.medicalnewstoday.com/articles/322857.php

Sokol post touches on the subject and gives a comprehensive overview of research:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=143320176&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=143320176&txt2find=autophagy

Autophagy was discussed in September 2018 at the New York Academy of Sciences one-day symposium
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=143337580&txt2find=autophagy

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145735099&txt2find=autophagy
The above links to non public research by Ashutosh Kumar, I found these links:
https://www.eurekalert.org/pub_releases/2018-12/bsp-aam122618.php

More on Dr. Kumar and his line of research:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147423162

Posts on autophagy and mitochondrial dysfunction studies being done by Dr. Ashutosh Kumar
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147422690
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147423162
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GABA:

GABA mentioned in the release of the first Rett Syndrome trial results:
"Additionally, after seven weeks of treatment, blood levels of the neurotransmitter glutamate decreased significantly, while levels of another neurotransmitter, GABA, or gamma-aminobutyric acid, increased significantly. A neurotransmitter is a chemical molecule that allows nerve cells to communicate. In Rett syndrome, there tend to be abnormally high glutamate levels and abnormally low GABA levels. As such, these results suggest a “balancing” of neurotransmitter levels."

https://rettsyndromenews.com/2019/09/19/preliminary-trial-data-anavex-2-73-rett-syndrome-suggest-safety-efficacy/

https://rettsyndromenews.com/author/marisa-wexler/

Discussion following the above:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151224598
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151171967
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151226208
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151265068
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151276120
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151324230
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151361598
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151361805
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151364314


Fluoroquinolones, benzodiazapenes, GABA, motochondiral damage:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146867284
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146867900

____________________________________________________________________________________________________________
GLUTAMATE AND GLUTAMINE:

Researching glutamate induced cytotoxicity, article:
https://www.frontiersin.org/articles/10.3389/fncel.2015.00091/full

Plasma Glutamate and Glutamine Levels
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151182940

Plasma Glutamate and GABA
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151364314
____________________________________________________________________________________________________________
BDNF:

"AdministraCon of ANAVEX 2-73 in the Fragile X Fmr1 KO mouse significantly restores hippocampal BDNF expression to the same levels observed in vehicle-treated wildtype mice (p<0.05, KO vehicle vs. KO ANAVEX 2-73)" slide of the presentation below:
http://www.anavex.com/wp-content/uploads/2017/05/Anavex-Angelman-FX-Rett-conference-update-2017-May-2017-final.pdf

What is BDNF?
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=148132680

ANAVEX 2-73 Normalizes Hippocampal BDNF Expression
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=148132992
__________________________________________________________________________________________________________________
ENDOCANNABINOID SYSTEM:

National Institute on Drug Abuse (NIDA/NIH) 2016 pesentation on the endocannabinoid system (>1 hr)

From dadofmarcmax 10/24/18
HOMEOSTATIC NETWORKING: THE ROLE OF PHYTOCHEMISTRY, THE ENDOCANNABINOID SYSTEM AND POTENTIAL FUTURE THERAPEUTICS
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=144438361

Comments on Cbd and Anavex from Cbdpotential:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146337883

Cannabanoid receptors
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146262610

dadofmarcmax on endocannabanoid system:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=144438361
____________________________________________________________________________________________________________
MITOCHONDRIAL DYSFUNCTION:

see also genetics section

The Role of Mitochondria in Aging and Disease - David Sinclair (from Investor2014)

The Fenton Reaction - one way mitochondria become dysfunctional.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=151136991

Mitochondrial Calcium Transport: New Theory of Alzheimer's (from
Talon38)
https://www.biospace.com/article/promising-new-theory-of-alzheimer-s-disease/?utm_campaign=GenePool&utm_source=hs_email&utm_medium=email&utm_content=76437862&_hsenc=p2ANqtz-8aWL2DvavYwbV4lhaeQeHLEaaUjjrwRfm7KDNTaBiSfoLm7tU7lByUOZ-eCzL7toZ-99lhpj7RODeP0pBvgC760FZ2dw&_hsmi=76437862

Commonly prescribed drugs are tied to nearly 50% higher dementia risk in older adults, study says (from kevli33).
https://www.cnn.com/2019/06/24/health/dementia-risk-drug-study/index.html

Mitochondrial dysfunction as a result of drugs and man made environmental toxins:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=142383333

ROS, mitochodira, and 2-73
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=142698154

Protein Misfolding and Accumulation as Root Cause in Neurodegeneration:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=1474176602-73

Misfolded proteins in cardomyopathy:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=148733003

Dangerous medicines and mitochondrial dysfunction:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=142393634

Fluoroquinolones, benzodiazapenes, GABA, motochondiral damage:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146867284
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146867900

Mitochondrial dysfunction, calorie restriction, aging, evolution and genetics:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821041/

Could Disposing of Damaged Mitochondria Treat Alzheimer’s Disease? (from Investor2014)
https://www.alzforum.org/news/research-news/could-disposing-damaged-mitochondria-treat-alzheimers-disease

Autism and Mitochondrial dysfuncution
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147104490

CVD and mitochondrial dysfunction:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146829394&txt2find=neurotransmitters

Envoiromental and pharmaceutical causes of mitochondrial dysfunction COMT gene:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147602552
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147602754
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147603103