UConn Health Center
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
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)
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...
1 Recommendation
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.
1 Recommendation
University of Texas Southwestern Medical Center
Oxidative stress is a factor in OSA, which has high co morbidity with depression.
Marlow
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.
Marlow
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?
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.
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
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.
Marlow
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
Marlow
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?
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.
