tag:blogger.com,1999:blog-8964719845369935777.post5335541923413354161..comments2024-03-27T21:23:40.339-04:00Comments on Chemjobber: Letter to the editor: who to believe on Alzheimer's? Chemjobberhttp://www.blogger.com/profile/15932113680515602275noreply@blogger.comBlogger5125tag:blogger.com,1999:blog-8964719845369935777.post-82142883994579101972015-08-12T01:29:27.675-04:002015-08-12T01:29:27.675-04:00An addition: the overactivation of receptor tyrosi...An addition: the overactivation of receptor tyrosine kinases can also lead to Alzheimer's disease. Lane Simoniannoreply@blogger.comtag:blogger.com,1999:blog-8964719845369935777.post-10691557398227274612015-08-12T01:26:05.251-04:002015-08-12T01:26:05.251-04:00Thanks for "paging me", otherwise I woul...Thanks for "paging me", otherwise I would not have seen this insightful and very important piece.<br /><br />Eleven years of studying this disease as a not scientist has lead to an important conclusion:<br /><br />It does not matter how much hyperphosphorylated tau, amyloid oligomers or amyloid plaques a person has in their brain as long as oxidants are being scavenged. Thus two people may have similar levels of each of these--one without Alzheimer's disease and one with Alzheimer's disease.<br /><br />When the oxidant peroxynitrite stops being scavenged, hyperphosphorylated tau is permanently nitrated which inhibits neurotransmissions and the transport of nutritents. When amyloid oligomers are nitrated they are converted into amyloid plaques. Amyloid plaques absorb copper and zinc which prevents (or limits) the further production of hydrogen peroxide.<br /><br />The pathways leading to oxidative stress, amyloid, and hyperphosphorylated tau are intertwined. All begin with the overactivation of g protein-coupled receptors (or the direct activation of g proteins) and the subsequent activation of phospholipase C. The then release of intracellular calcium leads to the production of amyloid oligomers whereas the then activation of protein kinase C leads to the production of peroxynitrites. Either pathway can lead to the hypeprhosphorylation of tau. <br /><br />If you inhibit the pathways that lead to the formation of oligomers, plaques, or hyperphosphorylated tau you may slow down the progression of the disease early on, but if you focus on removing the oligomers, plaques, or hyperphosphorylated tau you have done little to treat the disease. If you prevent the formation of peroxynitrites, scavenge them, and reverse part of their oxidative and nitration damage (among other things oxidation and/or nitration inhibit the synthesis and release of neurotransmitters involved in short-term memory, sleep, mood, social recognition, and alertness, reduce antioxidant levels in the brain, restrict blood flow and limit the transport of glucose in the brain which can lead to apathy, wandering, and delusions, prevent the regeneration of neurons in the hippocampus, can lead to hallucinations via the overactivation and then deactivation of NMDA receptors, and lead to the death of neurons) then you can not only inhibit the progression of Alzheimer's disease you can partially reverse it.<br /><br />The best peroxynitrite scavengers are methoxyphenols because the methoxy group increases the donation of hydrogen atoms and electrons from phenols (ONOO- + 2h+ + 2e-=NO2- +H20). Water is a de-nitrating agent and hydrogen donation also partially reverses oxidation. Small-scale clinical trials using the methoxyphenol eugenol in rosemary essential oil via aromatherapy (Jimbo, et al. 2009) and the methoxyphenol syringic acid and ferulic acid in panax ginseng (Heo, 2011) have resulted in the partial reversal of Alzheimer's disease.<br /><br />Once the paradigm shifts from amyloid and hyperphosphorylated tau as the cause of Alzheimer's disease to oxidation and nitration as the cause of Alzheimer's disease, then the path to the effective treatment of the disease becomes wide open.Lane Simoniannoreply@blogger.comtag:blogger.com,1999:blog-8964719845369935777.post-11626245325847660202015-08-07T20:57:35.417-04:002015-08-07T20:57:35.417-04:00" "I don't understand Alzheimer'..." "I don't understand Alzheimer's biology well enough to have an opinion on this letter." None of us do."<br /><br />I used to have a pretty good handle on it, but I've forgotten most of what I knew.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-8964719845369935777.post-63279905147372299482015-07-30T23:46:04.057-04:002015-07-30T23:46:04.057-04:00paging lane simonian paging lane simonian Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-8964719845369935777.post-48102971645706132092015-07-27T12:31:38.412-04:002015-07-27T12:31:38.412-04:00CJ: Thanks for the candor when you mention that ...CJ: Thanks for the candor when you mention that .."I don't understand Alzheimer's biology well enough to have an opinion on this letter." None of us do. It is my gut feeling that everyone who are working on it does not know it either! Right or wrong people do get funded and when it comes to proposing some novel ideas or concept for treating AD. Treating Rheumatoid Arthritis sometime back was difficult until we had Disease-Modifying Drugs (DMARDs). Knowing how complicated RA was in the past, I see a similar outcome for AD. Just a matter of trying it out in clinical setup! Anonymousnoreply@blogger.com