20th Sep, 2015
Ladoke Akintola University of Technology
Question
Asked 9th May, 2014
Is depression a neurodegenerative disease? Is oxidative stress a target for novel antidepressant?
Although mood disorders are not typical neurodegenerative disease, several studies have demonstrated that neural progression, reduced neurogenesis and neuroplasticity, and cell death occurs in some patients with mood disorders.
Most recent answer
YES!
Although many diseases have been associated with oxidative stress and the mechanisms have been well established. These neurodegenerative disorders have been linked with accumulation of malondialdehyde (MDA) (a potential marker of oxidative stress) which is the result of lipid peroxidation. Amyloid precursor proteins (APP), beta-amyloid protein (BAP) aggregation at the hypocampal portion of the brain had been proved to be a result of this lipid peroxidation process. Cholinergic related enzymes (acethylcholinesterase and butyrylcholinesterase) also have been linked with neurodegenerative disorders like (memory loss and diabetic encephalopathy). Drugs or pure compounds that could inhibit these targets (MDA, APP, BAP, AchE, BchE) would present potential remedy to the management/treatment of these disorders.
All Answers (15)
considering that oxidative stress is considered less and less plausible in many conditions, I would rather go for something more up-to-date...
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depression is considered in many articles as a neurodegenerative disease and oxidative stress is involved in the pathogenesis of several neurological and neurodegenerative disorders such as AD, Parkinson’s disease. I think it may be useful to evaluate the oxidative stress statut considering the fact that oxidative stress defines the neuroprotective properties of certains compounds.
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Oxidative stress is usually cited as the cause of death of dopaminergic neurons in Parkinson's disease, of which apathy and depression are frequent symptoms. α-Synuclein, the protein associated with tangles in PD and in Lewy Body dementia, is also inflammatory, at least in some form(s). Nevertheless the evidence is confusing and sometimes contradictory and I feel that oxidative stress is over-used to account for damage to biochemical structures and functions. Life has coexisted with free oxygen in the atmosphere for about 1.5 billion years and has thrived on it for the last 600 million years. It would be astonishing if natural selection had not provided us with robust defenses against oxidative stress. There is evidence indeed that oxidative stres is beneficial and one of the reasons for the benefits of exercise, which increases the generation of oxidative species, is due to their ability to degrade waste material in he brain and hasten its removal.
Inflammation is different and seems to be a significant factor in PD and in other nerodegenerative disease, notably Alzheimer's.
Li - Do you mean by "long term" and "chronic" something that is different from what is described in the references that I have cited? If so can you explain what it is?
As we all known, normal oxidative stress and inflammation are benefical,.But when there is an imbalance between increased ROS/RNS and lowered antioxidant defences, bad oxidative stress may occur. Inflammation is the same.
Dear Ruipeng Li.
There are many researches that links oxidative stress to neurodegenerative disorders as stated above. As far as chronic inflammation, ROS/RNS and oxidative stress is concerned, I say yes. For this I suggest you to refer "diabetes induced neurodegenerative disorders or diabetes induced depression. Since diabetic neuronal complication (depression also) are the outcome of excessive oxidative and inflammatory stress, this may work
Dear Ruipeng Li,
You ask if oxidative stress a target is for novel antidepressant. I like that thought. But later you refer to chronic inflammation. I think those two processes need different approaches when it comes to treatment.
The difficulty with 'oxidative stress' and 'inflammation' is that research mostly shows asssciation and the putative mechanism of cause and effect is conjectured, as it so often is in medical research, partiularly in neurodegenerative diseases where the affected organ is inaccessible (eg the role of beta-amyloid protein tangles in Alzheimer's). As a consequence most therapeutic trials are of the "let's try this and see if it works!" type. It rarely does and we learn nothng. Too much "knowledge" is nothing of the sort but is accepted as fact because it sounds plasible and has not been disproved.
There is a place for speculation and conjecture providing it is made absolutely clear that they are not established facts but ideas and possiblities. An individual's sincere conviction thata hypothesis is correct is not a proof.
2 Recommendations
Lawrence - Is this related to the recent report that anti-retroviral drugs used to treat HIV also improve patients with MS? Or that viral or some bacterial antigens mimic host proteins and provoke an autoimmune response?
YES!
Although many diseases have been associated with oxidative stress and the mechanisms have been well established. These neurodegenerative disorders have been linked with accumulation of malondialdehyde (MDA) (a potential marker of oxidative stress) which is the result of lipid peroxidation. Amyloid precursor proteins (APP), beta-amyloid protein (BAP) aggregation at the hypocampal portion of the brain had been proved to be a result of this lipid peroxidation process. Cholinergic related enzymes (acethylcholinesterase and butyrylcholinesterase) also have been linked with neurodegenerative disorders like (memory loss and diabetic encephalopathy). Drugs or pure compounds that could inhibit these targets (MDA, APP, BAP, AchE, BchE) would present potential remedy to the management/treatment of these disorders.
Similar questions and discussions
Can probiotics (eg yoghurt) activate the anti-aging gene Sirtuin 1 with relevance to the treatment of Alzheimer’s disease?
The relevance of the Microbiota-Gut-Brain axis to Alzheimer’s and neurodegenerative diseases needs extensive analysis. The various articles indicate that there are various questions with relevance to microbiota-gut-brain axis that are relevant to the pathology, pathogenesis and treatment of neurodegnerative diseases.Several mechanistic studies are required to determine the underlying mechanisms for effective and safe probiotic treatment for AD and probiotic benefits remain to determined. The relevance of gut dysbiosis may induce inflammatory responses that may be the cause of the induction of the pathogenesis of AD and relevance of diet (unhealthy diets), probiotics and gut microbiota should be carefully assessed. The meta-analysis studies indicate that probiotics reduce inflammation and oxidative stress and enhances cognition in AD and MCI individuals. The effects of different types of probiotics on amyloid formation and deposition needs to be evaluated and probiotic mixture therapy may be unsafe. The safety of probiotic therapy for AD patients require investigation with relevance to neuron reprogramming and programmed cell death in AD. The risk of unsafe microbiota and probiotic use may lead to the inactivation of the anti-aging gene Sirtuin 1 and the generation of uncontrolled short chain fatty acid release that promote amyloid beta plaque formation.
The concerns with relevance to the induction of dyslipidemia and the role of safety of diet-microbiota-brain axis should be carefully assessed with relevance to the cholesterol-AD connections. The prebiotic, symbiotic and probiotic formulations should be carefully assessed for bacterial composition and living microorganisms such as gram negative and positive. The release of bacterial lipopolysaccharides (LPS) from gram negative bacteria needs to be controlled and the content of gram negative bacteria carefully assessed in these prebiotic, symbiotic and probiotic formulations. Unhealthy diets contain end products such as LPS and diets should be carefully assessed for LPS contents since LPS has been associated with the inactivation of Sirtuin 1. The gut microbiota based therapy is in progress and the relevance to the treatment of brain diseases such as AD is limited. The benefits, limitations and safety of gut microbiota and probiotics on Alzheimer’s disease needs to be placed under systematic review with relevance to dietary regulation and postbiotic supplementation that have the implications for amyloidosis and neurodegeneration. The role of probiotic therapies to create a health gut environment by balancing bacterial populations may require the activation of the anti-aging gene Sirtuin 1 to reverse the pathogenesis of Alzheimer’s disease. The literature indicates that yogurt is a prime source for probiotics and provide a healthy balance of live bacteria to provide health benefits to individuals in various countries of the world. However a recent article indicates that within 12 hours yoghurt can grow gram negative bacteria. The gram negative bacteria in yoghurt depending on daily or weekly intake can generate high levels of plasma LPS with relevance to prebiotic, synbiotic and probiotic quality products and ill health. Yoghurt products may need to be assessed for gram negative bacteria populations and LPS to determine the quality control of these products for international communities.
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