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

20th Sep, 2015
Temitope Isaac Adelusi
Ladoke Akintola University of Technology
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)

9th May, 2014
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...
1 Recommendation
9th May, 2014
Mireille Kameni
THE 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
10th May, 2014
Imran Shuja Khawaja
University of Texas Southwestern Medical Center
Oxidative stress is a factor in OSA, which has high co morbidity with depression.
10th May, 2014
Ruipeng Li
China Pharmaceutical University
What about inflammation?
10th May, 2014
Stephen Warren
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.
11th May, 2014
Ruipeng Li
China Pharmaceutical University
I refer to the chronic inflammation and long-term oxidative stress.
11th May, 2014
Stephen Warren
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?
12th May, 2014
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.
15th May, 2014
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
2nd Jul, 2014
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. 
3rd Jul, 2014
Stephen Warren
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
30th Aug, 2014
Stephen Warren
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?
20th Sep, 2015
Temitope Isaac Adelusi
Ladoke Akintola University of Technology
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

Could Superoxide Dismutase therapy be beneficial for neurodegenerative disorders and antioxidant genes?
Discussion
5 replies
  • Annwyne HouldsworthAnnwyne Houldsworth
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.
Can probiotics (eg yoghurt) activate the anti-aging gene Sirtuin 1 with relevance to the treatment of Alzheimer’s disease?
Question
3 answers
  • Ian J MartinsIan J Martins
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.
📷
RELEVANT REFERENCES:
A. Marzban A, Rahmanian V, Marzban A, Ramezani Siakhulak F. The Role of Probiotics in Improving Alzheimer's Disease. JNFS. 2022; 7 (2) :136-138.
B. de Rijke TJ, Doting MHE, van Hemert S, De Deyn PP, van Munster BC, Harmsen HJM, Sommer IEC. A Systematic Review on the Effects of Different Types of Probiotics in Animal Alzheimer's Disease Studies. Front Psychiatry. 2022 Apr 27;13:879491.
C. Guo L, Xu J, Du Y, Wu W, Nie W, Zhang D, Luo Y, Lu H, Lei M, Xiao S, Liu J. Effects of gut microbiota and probiotics on Alzheimer's disease. Transl Neurosci. 2021 Dec 27;12(1):573-580.
D. Ji HF, Shen L. Probiotics as potential therapeutic options for Alzheimer's disease. Appl Microbiol Biotechnol. 2021 Oct;105(20):7721-7730.
E. D’Argenio V, Sarnataro D (2021) Probiotics, prebiotics and their role in Alzheimer’s disease. Neural Regen Res 16(9):1768-1769.
F. Bonfili L, Cuccioloni M, Gong C, Cecarini V, Spina M, Zheng Y, Angeletti M, Eleuteri AM. Gut microbiota modulation in Alzheimer's disease: Focus on lipid metabolism. Clin Nutr. 2022 Mar;41(3):698-708.
G. Naomi, R.; Embong, H.; Othman, F.; Ghazi, H.F.; Maruthey, N.; Bahari, H. Probiotics for Alzheimer’s Disease: A Systematic Review. Nutrients 2022, 14, 20.
H. Arora K, Green M, Prakash S. The Microbiome and Alzheimer's Disease: Potential and Limitations of Prebiotic, Synbiotic, and Probiotic Formulations. Front Bioeng Biotechnol. 2020 Dec 14;8:537847. doi: 10.3389/fbioe.2020.537847.
I. Peterson CT. Dysfunction of the Microbiota-Gut-Brain Axis in Neurodegenerative Disease: The Promise of Therapeutic Modulation With Prebiotics, Medicinal Herbs, Probiotics, and Synbiotics. J Evid Based Integr Med. 2020 Jan-Dec;25:2515690X20957225.
J. Kincaid HJ, Nagpal R, Yadav H. Diet-Microbiota-Brain Axis in Alzheimer's Disease. Ann Nutr Metab. 2021;77 Suppl 2:21-27. doi: 10.1159/000515700.
K. Alessio Vittorio Colombo Rebecca Katie Sadler Gemma Llovera Vikramjeet Singh Stefan Roth Steffanie Heindl Laura Sebastian Monasor Aswin Verhoeven Finn Peters Samira Parhizkar Frits Kamp Mercedes Gomez de Aguero Andrew J MacPherson Edith Winkler Jochen Herms Corinne Benakis Martin Dichgans Harald Steiner Martin Giera Christian Haass Sabina Tahirovic Arthur Liesz. (2021) Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition. eLife 10:e59826.
L. Anti-Aging Genes Improve Appetite Regulation and Reverse Cell Senescence and Apoptosis in Global Populations. Advances in Aging Research, 2016, 5, 9-26
N. Single Gene Inactivation with Implications to Diabetes and Multiple Organ Dysfunction Syndrome. J Clin Epigenet. Vol. 3 No. 3:24.
O. Sirtuin 1, a Diagnostic Protein Marker and its Relevance to Chronic Disease and Therapeutic Drug Interventions”. EC Pharmacology and Toxicology 6.4 (2018): 209-215.
P. Nutritional diets accelerate amyloid beta metabolism and prevent the induction of chronic diseases and Alzheimer’s disease. Photon ebooks. 2015.
Q. Wassenaar TM, Zimmermann K. Lipopolysaccharides in Food, Food Supplements, and Probiotics: Should We be Worried? Eur J Microbiol Immunol (Bp). 2018 Aug 21;8(3):63-69.
R. The Future of Genomic Medicine Involves the Maintenance of Sirtuin 1 in Global Populations. Int J Mol Biol . 2017. 2(1): 00013.
S. Bacterial Lipopolysaccharides and Neuron Toxicity in Neurodegenerative Diseases. Neurology Research and Surgery. 2018; 1(1): 1-3.
T. C.J. Hervert, N.H. Martin, K.J. Boor, M. Wiedmann. Survival and detection of coliforms, Enterobacteriaceae, and gram-negative bacteria in Greek yogurt, Journal of Dairy Science, Volume 100, Issue 2, 2017, Pages 950-960.
U. Fisberg M, Machado R. History of yogurt and current patterns of consumption. Nutr Rev. 2015 Aug;73 Suppl 1:4-7.

Related Publications

Got a technical question?
Get high-quality answers from experts.