Plasmologens for Neuroregeneration

[Plumster]

Plasmalogens Eliminate Aging-Associated Synaptic Defects and Microglia-Mediated Neuroinflammation in Mice

Neurodegeneration is a pathological condition in which nervous system or neuron losses its structure, function, or both leading to progressive neural degeneration. Growing evidence strongly suggests that reduction of plasmalogens (Pls), one of the key brain lipids, might be associated with multiple neurodegenerative diseases, including Alzheimer’s disease (AD). Plasmalogens are abundant members of ether-phospholipids. Approximately 1 in 5 phospholipids are plasmalogens in human tissue where they are particularly enriched in brain, heart and immune cells. In this study, we employed a scheme of 2-months Pls intragastric administration to aged female C57BL/6J mice, starting at the age of 16 months old. Noticeably, the aged Pls-fed mice exhibited a better cognitive performance, thicker and glossier body hair in appearance than that of aged control mice. The transmission electron microscopic (TEM) data showed that 2-months Pls supplementations surprisingly alleviate age-associated hippocampal synaptic loss and also promote synaptogenesis and synaptic vesicles formation in aged murine brain. Further RNA-sequencing, immunoblotting and immunofluorescence analyses confirmed that plasmalogens remarkably enhanced both the synaptic plasticity and neurogenesis in aged murine hippocampus. In addition, we have demonstrated that Pls treatment inhibited the age-related microglia activation and attenuated the neuroinflammation in the murine brain. These findings suggest for the first time that Pls administration might be a potential intervention strategy for halting neurodegeneration and promoting neuroregeneration.

The full article is here.

Nice to have Goodenowe's research confirmed.

[AnnaM]

Plasmalogens Eliminate Aging-Associated Synaptic Defects and Microglia-Mediated Neuroinflammation in Mice

These findings suggest for the first time that Pls administration might be a potential intervention strategy for halting neurodegeneration and promoting neuroregeneration.

The full article is here.

Nice to have Goodenowe's research confirmed.

Thank you Plumster for posting this! It's exciting when another "square of the quilt" is filled in.
Best, AnnaM

[MoJoe]

With respect, it is not Goodenowe's research confirmed. It is research by many who went before him confirmed . In fact he has suggested that supplements cannot work due to the fragility of the ethanolamine plasmalogen molecule within the stomach environment. (The workaround if that was correct is an enteric delivery.) That has been firmly debunked by a number of articles. Naturally he is keen to sell his alkyglycerols but to suggest supplements don't work is a bridge to far. We have been an advocate for, and making ethanolamine plasmalogens supplements,since 2017, further it was established by lipid scientists that the lack of ethanolamine plasmalogens was the cause of AD before he came on the scene.

[Plumster]

With respect, it is not Goodenowe's research confirmed. It is research by many who went before him confirmed . In fact he has suggested that supplements cannot work due to the fragility of the ethanolamine plasmalogen molecule within the stomach environment. (The workaround if that was correct is an enteric delivery.) That has been firmly debunked by a number of articles. Naturally he is keen to sell his alkyglycerols but to suggest supplements don't work is a bridge to far. We have been an advocate for, and making ethanolamine plasmalogens supplements,since 2017, further it was established by lipid scientists that the lack of ethanolamine plasmalogens was the cause of AD before he came on the scene.

Thanks for correcting me, MoJoe! I think he has just taken up more space on this forum and so his name is known here. Many kudos for your work!!

[Banch]

I recall reviewing at least a couple of articles that indicated that plasmalogens open the blood-brain barrier. In one article, this ability was touted as useful in drug testing. This concerned me, given my understanding that LPS and other pathogens, once in the CNS, activate microglia resulting in neuroinflammation. I welcome any comment regarding this observation and concern. If helpful, I will find examples of such articles and circle back.

[TheresaB]

I recall reviewing at least a couple of articles that indicated that plasmalogens open the blood-brain barrier. In one article, this ability was touted as useful in drug testing.

That's interesting, I've read many articles on factors that open/degrade the blood-brain barrier but don't ever recall plasmalogens being cited among them. In fact, I would think just the opposite seeing as how plasmalogens are a critical component of neuromembranes helping with cellular structure. Can you happen to dig up those articles and share?

I would also be interested in any articles regarding plasmalogens being used to open the BBB for drug testing. I don't recall any articles to that effect either, although nanoparticles are being thought to be promising for drug delivery, here are a few papers on that:

Nanoparticle-Guided Brain Drug Delivery: Expanding the Therapeutic Approach to Neurodegenerative Diseases

"Neurodegenerative diseases (NDs) represent a heterogeneous group of aging-related disorders featured by progressive impairment of motor and/or cognitive functions, often accompanied by psychiatric disorders. NDs are denoted as ‘protein misfolding’ diseases or proteinopathies, and are classified according to their known genetic mechanisms and/or the main protein involved in disease onset and progression. Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD) are included under this nosographic umbrella, sharing histopathologically salient features, including deposition of insoluble proteins, activation of glial cells, loss of neuronal cells and synaptic connectivity. To date, there are no effective cures or disease-modifying therapies for these NDs. Several compounds have not shown efficacy in clinical trials, since they generally fail to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells that greatly limits the brain internalization of endogenous substances. By engineering materials of a size usually within 1–100 nm, nanotechnology offers an alternative approach for promising and innovative therapeutic solutions in NDs. Nanoparticles can cross the BBB and release active molecules at target sites in the brain, minimizing side effects. This review focuses on the state-of-the-art of nanoengineered delivery systems for brain targeting in the treatment of AD, PD and HD."

Nanoparticles: A Hope for the Treatment of Inflammation in CNS

"Neuroinflammation, an inflammatory response within the central nervous system (CNS), is a main hallmark of common neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), among others. ... . Many drugs have shown promising therapeutic effects on microglia and inflammation. However, the blood–brain barrier (BBB)—a natural barrier preventing brain tissue from contact with harmful plasma components—seriously hinders drug delivery to the microglial cells in CNS. ... Recently, many NPs [nanoparticles] have been reported to be useful vehicles for anti-inflammatory drugs across the BBB to inhibit the over-activation of microglia and neuroinflammation. Therefore, NPs with good biodegradability and biocompatibility have the potential to be developed as an effective and minimally invasive carrier to help other drugs cross the BBB or as a therapeutic agent for the treatment of neuroinflammation-mediated neurodegenerative diseases. In this review, we summarized various nanoparticles applied in CNS, and their mechanisms and effects in the modulation of inflammation responses in neurodegenerative diseases, providing insights and suggestions for the use of NPs in the treatment of neuroinflammation-related neurodegenerative diseases."

Nanoparticle-Based Technology Approaches to the Management of Neurological Disorders

“In this article, insights into common neurological disorders and challenges of delivering CNS [Central Nervous System] drugs due to the presence of BBB is provided, before an in-depth review of nanoparticle-based theranostic strategies.”

[MarcR]

[...] he has suggested that supplements cannot work due to the fragility of the ethanolamine plasmalogen molecule within the stomach environment. (The workaround if that was correct is an enteric delivery.) That has been firmly debunked by a number of articles.

Perhaps you could cite a few of the articles so we can evaluate for ourselves?

[MoJoe]

Try the one at the top of this page for starters, "Plasmalogens Eliminate Aging-Associated Synaptic Defects and Microglia-Mediated Neuroinflammation in Mice". I will dig out some more tomorrow. Anecdotally 0.5 mg/capsule of Plasmalogen from NeuroRegain manages to survive, and seems to have a positive effect.

[TheresaB]

I recall reviewing at least a couple of articles that indicated that plasmalogens open the blood-brain barrier. In one article, this ability was touted as useful in drug testing.

I would also be interested in any articles regarding plasmalogens being used to open the BBB for drug testing. I don't recall any articles to that effect either, although nanoparticles are being thought to be promising for drug delivery, here are a few papers on that:

In addition to nanoparticles being promising for drug delivery through the Blood Brain Barrier, ultrasound also looks auspicious:

Non-invasive method to deliver drugs to the brain

"There are currently no non-invasive ways to minimize the damage to the blood-brain barrier and there is a big demand for methods to deliver large macromolecules to the brain safely to treat brain diseases.
In a new study researchers from the School of Biomedical Engineering & Imaging Sciences, in collaboration with the Noninvasive Surgery & Biopsy Laboratory led by Dr. James Choi at Imperial College London, have found that applying rapid short pulses (RaSP) of ultrasound can non-invasively deliver liposomes to the brain, across the blood-brain

barrier."

Evaluating Early Data on Focused Ultrasound for Patients With Alzheimer Disease

"For Alzheimer's, the blood-brain barrier has been a big problem in neuroscience to safely open, it’s possible if this can be done safely, it can be an effective way of clearing metabolites or pathological mediators. This study is looked at the first 10 subjects who underwent this procedure. “We demonstrated that we can safely, reversibly, and on-demand open the blood-brain barrier with focused ultrasound in mild Alzheimer's patients in all target regions—hippocampus, frontal lobes, and parietal lobes. There were no imaging adverse effects. There were no permanent clinical adverse effects, and the immediate blood-brain barrier opening was achieved within minutes of focused ultrasound treatment in the target region and resolved 24 to 48 hours later.“"

Focused Ultrasound Enables Precise Noninvasive Therapy

"Carnegie Mellon University’s He Lab is focusing on noninvasive neuroengineering solutions that not only provide diagnostic techniques, but also innovative treatment options. Their latest research has demonstrated that noninvasive neuromodulation via low-intensity ultrasound can have cell-type selectivity in manipulating neurons."

Focused ultrasound opening brain to previously impossible treatments

"Focused ultrasound, the researchers hope, could revolutionize treatment for conditions from Alzheimer's to epilepsy to brain tumors -- and even help repair the devastating damage caused by stroke."

[Gail]

Plasmalogens Eliminate Aging-Associated Synaptic Defects and Microglia-Mediated Neuroinflammation in Mice

Neurodegeneration is a pathological condition in which nervous system or neuron losses its structure, function, or both leading to progressive neural degeneration. Growing evidence strongly suggests that reduction of plasmalogens (Pls), one of the key brain lipids, might be associated with multiple neurodegenerative diseases, including Alzheimer’s disease (AD). Plasmalogens are abundant members of ether-phospholipids. Approximately 1 in 5 phospholipids are plasmalogens in human tissue where they are particularly enriched in brain, heart and immune cells.
Nice to have Goodenowe's research confirmed.

Plumster,

Thank you for the great reference. I wonder what amount of plasmalogen supplementain in humans will eliminate human age associated synaptic defects and human nueroinflammation?
I guess the answer to that is you need to be tested and then supplement until your total plasmalogen are at the 80th percentile?