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The Inter Relation of Free Radicals, Antioxidant Enzymes and Dementia (Lou Gehrig’s Disease(Amyotrophic Lateral Sclerosis))

Thursday, July 12, 2018 5:06
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Kyle J. Norton (Scholar) 

Dementia is a condition of neuro degeneration syndrome among elder, affecting memory, thinking, orientation, comprehension, calculation, learning capacity, language, and judgement. Over 47 millions of worldwide population are affected by the disease, mostly in the West.


The evaluation of the diseases by holistic medicine has been lacking, especially through conventional medicine research and studies.

Maintaining a balanced ratio of antioxidant and free radicals is an essential for our body to perform daily physiological function properly.

Truly, if our body is overwhelmed by over expression of free radicals, it will be weakened by oxidative stress, causing adversely altered lipids, proteins, and DNA that can trigger a number of human diseases(a), including dementia.

* Free radicals are unstable molecules that contain at least an unpaired electron with function  as oxidants or reductants by donated an electron to or accept an electron from other molecules to exhibit chain and domino’s effects.

Most common oxygen-containing free radicals found epidemiologically in induced chronic diseases, include hydroxyl radical, superoxide anion radical, hydrogen peroxide, oxygen singlet, hypochlorite, nitric oxide radical, and peroxynitrite radical.

According to the University of Texas Medical Branch,observation of patients with amyotrophic lateral sclerosis (ALS) indicated that free radicals play a role in expression of amyotrophic lateral sclerosis (ALS) through alternation of gene containing Cu,Zn superoxide dismutase (Cu,Zn-SOD).

Dr. Liu D said, “The selective degeneration of motor neurons in ALS may be caused by the high level of Cu,Zn-SOD present in and the large number of glutamatergic synapses projecting to these neurons”(b).

These selections of free radical in degeneration of motor neruons in ALS were attributed to free radical(mutation of Cu,Zn superoxide dismutase (Cu,Zn-SOD)) in long term induction of oxidative stress, according to the study involved167 ALS patients (aged 59+/-13 years), treated or not with riluzole, compared with 62 age-matched healthy control subjects (aged 60+/-11 years) simultaneously, conducted by Hôpital de la Salpêtrière(c).

Some researchers suggested that cell damage and homeostatic disruption caused by free radicals can be inhibited by targeting free radicals of all kinds of molecules in the body(a), including lipids, nucleic acids, and proteins, through improving antioxidant status in the body.

* Antioxidants is natural compound with function in inhibited molecules that cause oxidation before they can induce chains of domino’s reaction. 

* Antioxidants include those are produced by body tissue enzymes and externally dietary antioxidants intake from functional food sources.

Here are the summary of “The Battles of Free Radicals, Antioxidant Enzymes and Dementia (Lou Gehrig’s Disease(Amyotrophic Lateral Sclerosis))”

Free radicals and Dementia (Lou Gehrig’s disease)
Researchers found that glutamate in the synapses enhances the production of free radicals(77), due to its excitotoxicity, only in motor nerve cells but spares other nerve cells(74)(75) such as cells control senses and other body functions, causing disruption of astrocytes in regulated glutamate levels(76).

Antioxidants and Dementia (Lou Gehrig’s disease)
1. Vitamin B12 (methylcobalamin)
High doses of vitamin B12 as an antioxidant have shown to improve or slow muscle wasting in the later stages of patients with ALS disease(78)(79).

2. Vitamin E
Vitamin E protected against cell membranes from lipid peroxidation damage(80) in reduced the risk of breakdown of the cell membrane cause of ALS(81).

3. Superoxide dismutase enzyme 
Mutations in the superoxide dismutase enzyme can increase the risk ALS(82) in catalyzing the dismutation of superoxide into oxygen and hydrogen peroxide(83).

4. Cerebral cortex
Oxidative stress and DNA alternation triggered neurons damage(84) were found in elevating levels in mice with ALS(85).

5. Amino acids 
Diet high in amino acids as antioxidants have shown some promising effect in treating ALS(86)(87).

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Back to Kyle J. Norton Home page

Kyle J. Norton (Scholar) 
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it’s news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Named 50 of the best health Tweeters Canada – Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.

(a) Free radicals, antioxidants and functional foods: Impact on human health by V. Lobo, A. Patil, A. Phatak, and N. Chandra(PMC)
(b) The roles of free radicals in amyotrophic lateral sclerosis by Liu D(PubMed)
(c) Blood oxidative stress in amyotrophic lateral sclerosis by Bonnefont-Rousselot D1, Lacomblez L, Jaudon M, Lepage S, Salachas F, Bensimon G, Bizard C, Doppler V, Delattre J, Meininger V(PubMed)
(74) System xC- is a mediator of microglial function and its deletion slows symptoms in amyotrophic lateral sclerosis mice by Mesci P1, Zaïdi S1, Lobsiger CS1, Millecamps S1, Escartin C2, Seilhean D1, Sato H3, Mallat M1, Boillée S4.(PubMed)
(75) Microglia and motor neurons during disease progression in the SOD1G93A mouse model of amyotrophic lateral sclerosis: changes in arginase1 and inducible nitric oxide synthase by Lewis KE, Rasmussen AL, Bennett W, King A, West AK, Chung RS, Chuah MI1.(PubMed)
(76) Mutant disrupted-in-schizophrenia 1 in astrocytes: focus on glutamate metabolism by Abazyan S1, Yang EJ, Abazyan B, Xia M, Yang C, Rojas C, Slusher B, Sattler R, Pletnikov M.(PubMed)
(77) Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia by Globus MY1, Alonso O, Dietrich WD, Busto R, Ginsberg MD.(PubMed)
(78) Methyl Vitamin B12 but not methylfolate rescues a motor neuron-like cell line from homocysteine-mediated cell death. by Hemendinger RA1, Armstrong EJ 3rd, Brooks BR.(PubMed)
(79) [Clinical trials of ultra-high-dose methylcobalamin in ALS].[Article in Japanese] by Izumi Y1, Kaji R.(PubMed)
(80) Antioxidant effect of 4-nerolidylcatechol and α-tocopherol in erythrocyte ghost membranes and phospholipid bilayers. by Fernandes KS1, Silva AH, Mendanha SA, Rezende KR, Alonso A.(PubMed)
(81) Vitamin E serum levels and controlled supplementation and risk of amyotrophic lateral sclerosis by Michal Freedman D1, Kuncl RW, Weinstein SJ, Malila N, Virtamo J, Albanes D.(PubMed)
(82) Aggregation propensities of superoxide dismutase G93 hotspot mutants mirror ALS clinical phenotypes by Pratt AJ1, Shin DS1, Merz GE2, Rambo RP3, Lancaster WA4, Dyer KN3, Borbat PP5, Poole FL 2nd4, Adams MW4, Freed JH5, Crane BR2, Tainer JA6, Getzoff ED7.(PubMed)
(83) Hydrogen peroxide induce modifications of human extracellular superoxide dismutase that results in enzyme inhibition by Gottfredsen RH1, Larsen UG, Enghild JJ, Petersen SV.(PubMed)
(84) Oxidative DNA damage and alteration of glutamate transporter expressions in the hippocampal Ca1 area immediately after ischemic An SJ1, Kang TC, Park SK, Hwang IK, Cho SS, Chung MH, Won MH.(PubMed)
(85) Functional contribution of the transcription factor ATF4 to the pathogenesis of amyotrophic lateral Matus S1, Lopez E, Valenzuela V, Nassif M, Hetz C.(PubMed)
(86) Amino acids as biomarkers in the SOD1(G93A) mouse model of Bame M1, Grier RE, Needleman R, Brusilow WS.(PubMed)
(87) Branched-chain amino acids and amyotrophic lateral sclerosis: a treatment failure? The Italian ALS Study Group.[No authors listed](PubMed)

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