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Oxidation, nitration, hydrogen donation, Alzheimer's disease
Lane Simonian
Posted: Monday, August 31, 2020 10:09 PM
Joined: 12/12/2011
Posts: 4863


Oxidation (the loss of hydrogen atoms) and nitration (the addition of NO2) are likely the root causes of Alzheimer's disease.  Oxidation and nitration damage critical receptors, enzymes, and transport systems in the brain.  A couple of examples.  The oxidation of g protein-coupled receptors contributes to a loss of smell, distrurbed sleep, loss of social recognition, and the inability to retrieve short-term memories.  The nitration of the phosphatidyinositol-3 kinase enzyme, prevents the regeneration of neurons, synapses, and axons in the brain and inhibit neurotransmissions.  Oxidation and nitration also affects the activities of enzymes involved in the death of neurons.

The key to treating Alzheimer's disease is to find compounds that readily donate hydrogen atoms.  These compounds add hydrogen back to receptors, enzymes, and transport system, scavenge peroxynitrite, and in the process of scavenging peroxynitrite produce water which helps to de-nitrate proteins.  Among the substances that partially reverse oxidation, scavenge peroxynitrite, and de-nitrate proteins are panax ginseng, medicinal marijuana, essential oils via aromatherapy, and Anavex 2-73.  There is an urgent need to determine which substances are the best hydrogen donors and to test these substances for the treatment of Alzheimer's disease.  They can likely greatly slow down, stabilize, and in some aspects improve the conditions of people with Alzheimer's disease.


wolfewoman
Posted: Tuesday, September 1, 2020 10:21 PM
Joined: 1/1/2018
Posts: 208


Maybe crazy question but what about hydrogenated water? I bought tablets to drop nto my water.
Lane Simonian
Posted: Tuesday, September 1, 2020 10:46 PM
Joined: 12/12/2011
Posts: 4863


Not a crazy question at all.  Various forms of hydrogen have been suggested for the treatment of Alzheimer's disease including hydrogen-rich water.

The role of hydrogen in Alzheimer’s disease

Mechanisms of the Hydrogen Therapy in Alzheimer’s Disease


Inflammation and oxidative stress are recognized as the main causes of AD...hydrogen molecules such as hydrogen-rich water, hydrogen-rich saline or hydrogen inhalation exhibit anti-inflammatory and anti-oxidant effects in many studies.

And this one:

Lane Simonian
Posted: Tuesday, September 1, 2020 11:13 PM
Joined: 12/12/2011
Posts: 4863


A bit further afield and in mice, but still a useful study:

Protective effect of molecular hydrogen against oxidative stress caused by peroxynitrite derived from nitric oxide in rat retina

Results: H2 [molecular hydrogen in hydrogen-rich water, for instance] suppressed loss of mitochondrial membrane potential and apoptosis in retinal cells. Moreover, H2 decreased the tyrosine nitration level and suppressed oxidative stress damage in retinal cells...These findings suggest that H2 has a neuroprotective effect against retinal cell oxidative damage, presumably by scavenging peroxynitrite.

Conclusions: H2 reduces cellular peroxynitrite, a highly toxic reactive nitrogen species. Thus, H2 may be an effective and novel clinical tool for treating glaucoma and other oxidative stress-related diseases [i.e. Alzheimer's disease].



Lane Simonian
Posted: Saturday, January 2, 2021 3:31 PM
Joined: 12/12/2011
Posts: 4863


Research wise, the beginning of the year is great: you can type in a subject on Alzheimer's disease in google scholar and come up with a half dozen citations rather than several hundreds.  One of the first ones I found this year is a good one.

Neurogenesis versus neurodegeneration: the broken balance in Alzheimer’s disease

Accruing evidence indicates the role of systemic and brain metabolic aberrations, in addition to the canonical hallmarks, in AD pathogenesis (Polis and Samson, 2019). The up-to-date description of AD-associated pathology includes neuroinflammation, mitochondrial dysfunction, instigated apoptosis, and chronic oxidative stress. Of note, oxidative damage is one of the earliest events causing and following AD (Nunomura et al., 2001). Moreover, oxidative damage is strongly associated with neurodegenerative processes and it is a connecting factor between β-amyloidosis, τ-protein hyperphosphorylation, and neuronal loss. Oxidative stress due to the disbalance between generation and elimination of reactive oxygen species (ROS) plays a key role in β-amyloid-mediated cytotoxicity via a spectrum of molecular events that eventually lead to a substantial neuronal loss, which is a primary hallmark of AD, clinically manifesting in cognitive decline. In healthy individuals, excessive ROS production is counteracted by physiological antioxidant mechanisms that incessantly maintain redox homeostasis. However, these mechanisms are inadequate in the AD brain tissue and do not provide the necessary protection against highly reactive species, which disrupt membrane function, impair enzymes, break polysaccharides, and damage nucleic acids...

Adult neurogenesis is extremely responsive to the brain pathology and correlates with its severity. Neurogenesis counteracts neurodegeneration in the aging and AD brains by implicating neural progenitors in the repair mechanisms and replacement of nonfunctional brain tissue. However, the development of AD is followed by an increase in the imbalance between these two counterdirected processes. Notably, oxidative stress due to numerous factors seems to be the main cause of this imbalance. The AD brain is under gradually growing oxidative stress, leading to progressive neuron degeneration and, eventually, death and atrophy of susceptible areas. On the other hand, chronic oxidative stress causes neurogenesis decline that further aggravates clinical dementia, which becomes irreversible. Therefore, early diagnosis and preventive interventions targeted at neurovascular unit function and ROS elimination are the most promising approaches to combat the disease.

https://www.nrronline.org/article.asp?issn=1673-5374;year=2021;volume=16;issue=3;spage=496;epage=497;aulast=Polis

The same compounds (particularly peroxynitrite) that cause neuronal cell death through oxidation and nitration also prevent the regeneration of neurons through nitration.  Antioxidants which scavenge peroxynitrite produce water and water is a denitrating agents.  Thus effective antioxidants prevent or limit further neuronal cell death while promoting the regeneration of neurons.