Question
Asked 9 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

Temitope Isaac Adelusi
UConn Health Center
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)

Francesco Roselli
Ulm University
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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Mireille Kameni
University of Bamenda
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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Imran Shuja Khawaja
University of Texas Southwestern Medical Center
Oxidative stress is a factor in OSA, which has high co morbidity with depression.
Ruipeng Li
China Pharmaceutical University
What about inflammation?
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.
Ruipeng Li
China Pharmaceutical University
I refer to the chronic inflammation and long-term oxidative stress.
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?
Ruipeng Li
China Pharmaceutical University
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.
Vineet Mehta
Govt. College of Pharmacy Rohru
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
Maria Schenk
University of Groningen
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?
Temitope Isaac Adelusi
UConn Health Center
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. 

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Neurological disorders include a variety of conditions including Alzheimer’s, Motor Neuron and Parkinson’s disease, affecting longevity and quality of life and these have been associated with oxidative stress. Several of the chronic neurodegenerative pathologies of the central nervous system share some common features, such as oxidative stress, closely related to inflammation, synapse dysfunctions, protein misfolding, and defective autophagia. Sources of reactive oxygen species (ROS) that cause oxidative stress, relating oxidative damage with the pathogenesis of neurodegenerative disorders. Antioxidants can powerfully neutralise ROS and free radicals, decreasing oxidative damage. Antioxidant genes, like manganese superoxide dismutase (SOD-2) enzymes, can undergo epigenetic changes that reduce its expression, thus increasing oxidative stress in tissue or DNA can be altered by free radical damage. The epigenetic landscape of these genes can alter antioxidant function and can result in neurodegenerative disease. This imbalance of free radical production and antioxidant function increase the ROS that cause neuronal cell damage, often observed as an age-related event. Familial MND is associated with SOD-1 antioxidant gene polymorphism and function.
Increased antioxidant expression in mice is protective against ROS in neurons as is the exogenous supplementation of antioxidants. The associated manganese deficiency observed in Alzheimer’s suggests that this transition metal could be supplemented in deficient patients or SOD—2 therapy considered for age-related neurodegenerative disorders.
A new mimetic of SOD-2, Avasopasem manganese (GC4419 AVA), is described and suggested as putative treatment to reduce the oxidative stress that causes neurodegenerative diseases.

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