Biofilm-associated proteins: from the gut biofilms to neurodegeneration

 17 pages at the link which your competent? doctor will distill into EXACT PREVENTION PROTOCOLS, right? Oh no, NOTHING HAPPENED, LIKE USUAL!

Do you prefer your doctor and hospital incompetence NOT KNOWING? OR NOT DOING?

The reason you need dementia prevention: 

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.

3. A 20% chance in this research.   July 2013. 

Biofilm-associated proteins: from the gut biofilms to neurodegeneration

Authors:	Valle Turrillas, Jaione CSIC ORCID
Funders:	Agencia Estatal de Investigación (España) Ministerio de Ciencia e Innovación (España)
Keywords:	Amyloid Biofilm Biofilm-associated protein Gut microbiota α-synuclein
Issue Date:	Dec-2025
Publisher:	Taylor & Francis
Citation:	Gut Microbes 17(1): 2461721 (2025)
Abstract:	Human microbiota form a biofilm with substantial consequences for health and disease. Numerous studies have indicated that microbial communities produce functional amyloids as part of their biofilm extracellular scaffolds. The overlooked interplay between bacterial amyloids and the host may have detrimental consequences for the host, including neurodegeneration. This work gives an overview of the biofilm-associated amyloids expressed by the gut microbiota and their potential role in neurodegeneration. It discusses the biofilm-associated proteins (BAPs) of the gut microbiota, maps the amyloidogenic domains of these proteins, and analyzes the presence of bap genes within accessory genomes linked with transposable elements. Furthermore, the evidence supporting the existence of amyloids in the gut are presented. Finally, it explores the potential interactions between BAPs and α-synuclein, extending the literature on amyloid cross-kingdom interactions. Based on these findings, this study propose that BAP amyloids act as transmissible catalysts, facilitating the misfolding, accumulation, and spread of α-synuclein aggregates. This review contributes to the understanding of complex interactions among the microbiota, transmissible elements, and host, which is crucial for developing novel therapeutic approaches to combat microbiota-related diseases and improve overall health outcomes.
Publisher version (URL):	https://doi.org/10.1080/19490976.2025.2461721
URI:	http://hdl.handle.net/10261/396268
DOI:	10.1080/19490976.2025.2461721
ISSN:	1949-0976
E-ISSN:	1949-0984
User license:	https://creativecommons.org/licenses/by/4.0/
Source works:	The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.1080/19490976.2025.2461721© 2025 CSIC. Published with license by Taylor & Francis Group, LLC.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the AcceptedManuscript in a repository by the author(s) or with their consent.
Appears in Collections:	(IDAB) Artículos

Intracellular delivery of Parkin rescues neurons from accumulation of damaged mitochondria and pathological α-synuclein

You and your doctor should be following this research very closely because of your chance of getting Parkinsons. Does your doctor even know about that probability? It is only three years old.

Parkinson’s Disease May Have Link to Stroke March 2017 

The latest here:

Intracellular delivery of Parkin rescues neurons from accumulation of damaged mitochondria and pathological α-synuclein

1. Eunna Chung¹,*,
2. Youngsil Choi¹,*,
3. Jiae Park¹,
4. Wonheum Nah¹,
5. Jaehyung Park¹,
6. Yukdong Jung¹,
7. Joonno Lee¹,
8. Hyunji Lee¹,
9. Soyoung Park¹,
10. Sunyoung Hwang¹,
11. Seongcheol Kim¹,
12. Jongseok Lee¹,
13. Dongjae Min¹,
14. Junghwan Jo¹,
15. Shinyoung Kang¹,
16. Minyong Jung¹,
17. Phil Hyu Lee²,
18. H. Earl Ruley³ and
19. Daewoong Jo¹,†

See all authors and affiliations

Science Advances  29 Apr 2020:
Vol. 6, no. 18, eaba1193
DOI: 10.1126/sciadv.aba1193

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Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by mitochondrial dysfunction, Lewy body formation, and loss of dopaminergic neurons. Parkin, an E3 ubiquitin ligase, is thought to inhibit PD progression by removing damaged mitochondria and suppressing the accumulation of α-synuclein and other protein aggregates. The present study describes a protein-based therapy for PD enabled by the development of a cell-permeable Parkin protein (iCP-Parkin) with enhanced solubility and optimized intracellular delivery. iCP-Parkin recovered damaged mitochondria by promoting mitophagy and mitochondrial biogenesis and suppressed toxic accumulations of α-synuclein in cells and animals. Last, iCP-Parkin prevented and reversed declines in tyrosine hydroxylase and dopamine expression concomitant with improved motor function induced by mitochondrial poisons or enforced α-synuclein expression. These results point to common, therapeutically tractable features in PD pathophysiology, and suggest that motor deficits in PD may be reversed, thus providing opportunities for therapeutic intervention after the onset of motor symptoms.

TSRI researchers uncover culprit in Parkinson's brain cell die-off

You'll likely need this, so what is your doctor doing to prevent your Parkinsons risk?

Your Parkinsons risk:

Parkinson’s Disease May Have Link to Stroke

https://www.alphagalileo.org/ViewItem.aspx?ItemId=184225&CultureCode=en

05 March 2018 The Scripps Research Institute

Scientists have discovered a connection between neuronal death and Lewy bodies in Parkinson's disease.

An estimated 10 million people worldwide are living with Parkinson’s disease—an incurable neurodegenerative disorder that leads to an increasing loss of motor control. 

If we could peer into the brains of these patients, we’d see two hallmarks of the disease. First, we’d see a die-off of the brain cells that produce a chemical called dopamine. We’d also see protein clumps called Lewy bodies inside the neurons.

Corinne Lasmézas, DVM, PhD, a professor on the Florida campus of The Scripps Research Institute (TSRI), believes a key to treating Parkinson’s is to study possible links between these two phenomena.

Now her group has discovered a connection between neuronal death and Lewy bodies. The research, published recently in the journal Proceedings of the National Academy of Sciences, offers an explanation for why neurons die off in the first place.

‘This study identifies the missing link between Lewy bodies and the type of damage that’s been observed in neurons affected by Parkinson’s,” says Lasmézas, senior author of the  study. “Parkinson’s is a disorder of the mitochondria, and we discovered how Lewy bodies are releasing a partial break-down product that has a high tropism for the mitochondria and destroys their ability to produce energy.” 

Toxic protein travels to mitochondria to do damage

Lewy bodies were described a century ago, but it was not until 1997 that scientists discovered they were made of clumps of a misfolded protein called α-synuclein. When it’s not misfolded, α-synuclein is believed to carry out functions related to the transmission of signals between neurons. 

Lasmézas’ research focuses on neurological disorders caused by misfolded proteins, such as Alzheimer's, Parkinson’s, prion diseases, frontotemporal dementia and amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease). She uses lab models, including cell cultures and mice, to study these diseases. 

In the current study, Lasmézas and her team looked at cell cultures of neurons that were induced to accumulate fibrils made of misfolded α-synuclein, mimicking Lewy bodies in patients with Parkinson’s. They discovered that when α-synuclein fibrils are broken down, it often creates a smaller protein clump, which they named pα-syn* (pronounced “P-alpha-syn-star”).

“Sometimes the nerve cells can efficiently degrade the α-synuclein fibrils, but if they get overwhelmed, the degradation may be incomplete,” she explains. “And it turns out that the result of that partial degradation, pα-syn*, is toxic.” 

Diego Grassi, PhD, a research associate in Lasmézas’ lab, made this discovery by labeling the pα-syn* with an antibody so he could follow it throughout the cell after it was created. He observed that pα-syn* traveled and attached itself to the mitochondria. Further investigation revealed that once the pα-syn* attached, the mitochondria started to break down. These fragmented mitochondria lose their ability to carry an electrochemical signal and produce energy. 

The researchers followed up with an analysis of mouse and human brain samples. They confirmed the existence of pα-syn* in the dopamine-producing neurons.

“The Lewy bodies are big aggregates and they’re sitting in the cell, but they don’t come into direct contact with the mitochondria in the way pα-syn* does,” Lasmézas explains. “With Diego’s discovery, we’ve made a direct connection between the protein α-synuclein and the downstream effects that are observed when brain cells become damaged in Parkinson’s.”

Lasmézas plans to continue studying the connection between misfolded proteins and the destruction of mitochondria in neurons. “What we found may not be the only mechanism of toxicity, but we know it’s important,” she says. “This paper is about identifying where pα-syn* comes from and what it does to the mitochondria, but there’s obviously, mechanistically, a lot that we still don’t know.”

She says that these findings also have implications for designing treatments for Parkinson’s, noting that some drugs currently under development are focused on getting rid of larger fibrils that make up Lewy bodies.

“It’s important to be aware that when Lewy bodies are broken down, these toxic substances may be created,” Lasmézas says. In addition, she adds, the discovery of pα-syn* as an important component of the disease process points to a new target for creating drugs slowing disease progression. 

First author of the study, “Identification of a highly neurotoxic α-synuclein species inducing mitochondrial damage and mitophagy in Parkinson’s disease,” was Diego Grassi. Other authors were Shannon Howard, Minghai Zhou, Natalia Diaz-Perez, and Philip LoGrasso of The Scripps Research Institute; Nicolai T. Urban, Debbie Guerrero-Given, and Naomi Kamasawa of the Max Planck Florida Institute for Neuroscience; and Laura Volpicelli-Daley of the University of Alabama at Birmingham.

This research was funded by the National Institute of Neurological Disorders and Stroke (grant R01NS085223), the Michael J. Fox Foundation and the Saul and Theresa Esman Foundation.

Attached files

• 
  The new study was led by Corinne Lasmézas, PhD, and Diego Grassi, PhD, of the Florida campus of The Scripps Research Institute.

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• Full bibliographic information"Identification of a highly neurotoxic α-synuclein species inducing mitochondrial damage and mitophagy in Parkinson’s disease," by
  Diego Grassi, Shannon Howard, Minghai Zhou, Natalia Diaz-Perez, Nicolai T. Urban, Debbie Guerrero-Given, Naomi Kamasawa, Laura A. Volpicelli-Daley, Philip LoGrasso and Corinne Ida Lasmézas. Proceedings of the National Academy of Science, Feb. 2018

Asthma drug may thwart Parkinson’s disease - Salbutamol

You might very well need this so you better hope that this is followed up better than any stroke research is.

Parkinson’s Disease May Have Link to Stroke

Or are the stem cells better?

Injecting stem cells into the brain reverses Parkinson’s symptoms in monkeys

The newest here:

Asthma drug may thwart Parkinson’s disease - Salbutamol 

By Mitch LeslieAug. 31, 2017 , 2:00 PM

When people with asthma have trouble breathing, they may reach for an inhaler containing salbutamol, a drug that expands the airways. Salbutamol may have another beneficial effect—protecting against Parkinson’s disease. Individuals who inhaled the highest doses of salbutamol were about half as likely to develop the devastating neurological condition as those who didn’t take the drug, a study reveals.
“I’m sure it’s going to be a landmark paper,” says neurologist Joseph Jankovic of Baylor College of Medicine in Houston, Texas, who wasn’t involved in the research.
In Parkinson’s disease, gobs of the protein α-synuclein accumulate in certain brain cells and may kill them. Scientists have tried to craft drugs that speed the elimination of the protein or prevent it from clumping. Neurologist and genomicist Clemens Scherzer of Harvard Medical School in Boston and colleagues decided to try a different strategy. “We wanted to find a drug that could turn down the production of α-synuclein,” he says.

To identify promising compounds, the team grew human nerve cells in the lab and tested whether more than 1100 medications, vitamins, dietary supplements, and other molecules altered their output of α-synuclein. Three of the drugs that cut the protein’s production, including salbutamol, work by stimulating the b2-adrenoreceptor—a molecule on some body cells that triggers a variety of effects, including relaxing the airways. The researchers found that these drugs appear to alter how tightly the DNA containing the α-synuclein gene coils, and thus whether the gene is active.
Salbutamol is one of the world’s most frequently used drugs, and the researchers wondered whether people who took it were less likely to have Parkinson’s disease. “You need to have very large prescription databases with many years of follow-up to do this analysis,” Scherzer says. The researchers found such a database in Norway, which keeps records of all drugs prescribed for each of its 4.6 million residents. The disease was rare. Roughly 0.1% of people who didn’t use the drug developed Parkinson’s disease. The rate among people who used salbutamol was less than 0.04%. After the researchers corrected for factors such as age and education, they determined that Norwegians who had taken salbutamol at least once in their lives were about one-third less likely to develop Parkinson’s disease.
How much protection salbutamol provided depended on the dosage. Compared with Norwegians who didn’t use the drug, people who took the highest doses between 2004 and 2007 were about half as likely to get the disease in the subsequent 7 years. In contrast, patients who took the lowest doses had only slightly lower odds of developing Parkinson’s disease in that period, the researchers report online today in Science.
The results are “fascinating” and “come out of the blue,” says neurologist Anthony Lang of the University of Toronto in Canada. However, he has misgivings about the analysis of the Norwegian data because salbutamol’s influence on α-synuclein appears to be so powerful that it’s surprising we ever see a Parkinson’s patient with asthma, he says. Given that some people do have both diseases, other factors that correlate with salbutamol use might be affecting Parkinson’s disease susceptibility. “We have to take other possible explanations into account,” he says.
Researchers aren’t sure about the best way to harness the results to benefit patients. Clinical trials of salbutamol or related drugs are one possibility. However, none of these drugs is optimized to enter the brain, says neuroscientist Andrew West of the University of Alabama in Birmingham. “The drugs that are going to be ideal for targeting [α-synuclein] have yet to be developed.”
Scherzer says that any clinical trials are “a few years off.” He notes that 16 recent trials of potential Parkinson’s disease treatments have failed. He and his colleagues don’t want to have No. 17.

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doi:10.1126/science.aap8401

 

Caffeine Based Compounds Show Promise Against Parkinson’s

I've only written 107 posts on coffee and 49 on caffeine which means your doctor has missed writing the article; 'Coffee-based compounds show promise against stroke'. But then we already know your doctor and stroke hospital are totally incompetent against stroke.

Caffeine Based Compounds Show Promise Against Parkinson’s

Summary: Researchers have developed two caffeine based compounds that show promise in the fight against Parkinson’s disease.
Source: University of Saskatchewan.
A team of researchers from the University of Saskatchewan has developed two caffeine-based chemical compounds that show promise in preventing the ravages of Parkinson’s disease.
Parkinson’s disease attacks the nervous system, causing uncontrolled shakes, muscle stiffness, and slow, imprecise movement, chiefly in middle-aged and elderly people. It is caused by the loss of brain cells (neurons) that produce dopamine, an essential neurotransmitter that allows neurons to “talk” to each other.
The team focused on a protein called α-synuclein (AS), which is involved in dopamine regulation.
In Parkinson’s sufferers, AS gets misfolded into a compact structure associated with the death of dopamine-producing neurons. Worse, AS appears to act like a prion disease (for example, variant Creutzfeldt-Jacob or “mad cow”). In prion diseases, one mis-folded protein triggers mis-folding in others, spreading like falling dominos.
Jeremy Lee, a biochemist from the U of S College of Medicine, and Ed Krol from the College of Pharmacy and Nutrition led the team, which included researchers Troy Harkness and Joe Kakish from the U of S College of Medicine, as well as Kevin Allen from the Drug Discovery and Research Group in the College of Pharmacy and Nutrition.
“Many of the current therapeutic compounds focus on boosting the dopamine output of surviving cells, but this is effective only as long as there are still enough cells to do the job,” Lee said. “Our approach aims to protect dopamine-producing cells by preventing α-synuclein from mis-folding in the first place.”

In Parkinson’s sufferers, AS gets misfolded into a compact structure associated with the death of dopamine-producing neurons. Worse, AS appears to act like a prion disease (for example, variant Creutzfeldt-Jacob or “mad cow”). In prion diseases, one mis-folded protein triggers mis-folding in others, spreading like falling dominos. NeuroscienceNews.com image is for illustrative purposes only.

Although the chemistry was challenging, Lee explained the team synthesized 30 different “bifunctional dimer” drugs, that is, molecules that link two different substances known to have an effect on dopamine-producing cells. They started with a caffeine “scaffold,” guided by literature that shows the stimulant has a protective effect against Parkinson’s. From this base, they added other compounds with known effects: nicotine, the diabetes drug metformin, and aminoindan, a research chemical similar to the Parkinson’s drug rasagiline.
Using a yeast model of Parkinson’s disease, Lee and his team discovered two of the compounds prevented the AS protein from clumping, effectively allowing the cells to grow normally.
“Our results suggest these novel bifunctional dimers show promise in preventing the progression of Parkinson’s disease,” Lee said.

About this Parkinson’s disease research article

Funding: Funding for the research was provided through the Saskatchewan Health Research Foundation and the Natural Sciences and Engineering Research Council of Canada. The U of S Industry Liaison Office provided initial funding through its Proof of Concept Fund and has prepared a summary of the technology, inviting potential charitable funding and commercial partnerships to help develop it further.
Source: Jennifer Thoma – University of Saskatchewan

Original Research: Abstract for “Novel Dimer Compounds That Bind α-Synuclein Can Rescue Cell Growth in a Yeast Model Overexpressing α-Synuclein. A Possible Prevention Strategy for Parkinson’s Disease” by Joe Kakish, Kevin J.H. Allen, Troy A. Harkness, Edward Stanley Krol, and Jeremy Stuart Lee in ACS Chemical Neuroscience. Published online September 27 2016 doi:10.1021/acschemneuro.6b00209