A recent message (60053) mentioned working on a manuscript on how Rosetta@home has worked on a number of workunits relevant to diseases involving amyloids, of which two of the best known are Alzheimer's and type 2 diabetes.

https://boinc.bakerlab.org/rosetta/forum_thread.php?id=1177

I did a Yahoo search to find web sites relevant to amyloid diseases, and found too many of them to list here in the time I have left today, so I'll try to start listing them tomorrow.

For Alzheimer's, amyloid fibrils seem to be responsible for many of the symptoms. For type 2 diabetes, amyloid fibrils seem to be responsible for loss of the ability of the beta islets to produce insulin, and therefore the progression to requiring insulin injections; it's not clear if they are also involved in the insulin resistance typical of type 2 diabetes.

Amyloid fibrils are also involved in a number of rare diseases.

So far I've found the names of two substances said to interfere with amyloid formation:

phenol red
nattokinase

Amyloids and phenol red:


Drusen deposits associated with aging and age-related macular
degeneration contain nonfibrillar amyloid oligomers

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16453022


The Role of Phe in the Formation of Well-Ordered Oligomers of
Amyloidogenic Hexapeptide (NFGAIL) Observed in Molecular Dynamics
Simulations with Explicit Solvent

http://www.cell.com/biophysj/fulltext/S0006-3495(05)73342-7


Phenol Red Interacts with the Protofibril-Like Oligomers of an
Amyloidogenic Hexapeptide NFGAIL through Both Hydrophobic and
Aromatic Contacts

http://www.cell.com/biophysj/fulltext/S0006-3495(06)72078-1


Small Molecule Inhibitors of Aggregation Indicate That Amyloid
Oligomerization and Fibrillization Pathways Are Independent and
Distinct

http://www.jbc.org/cgi/content/full/282/14/10311


Vitamin E But Not 17-Estradiol Protects against Vascular Toxicity
Induced by -Amyloid Wild Type and the Dutch Amyloid Variant

http://www.jneurosci.org/cgi/content/full/22/8/3081


Amyloid beta oligomers induce impairment of neuronal insulin
receptors

http://www.northwestern.edu/neurobiology/faculty/Klein_pubs/amyloid_beta_oligimers.pdf


Acceleration of Amyloid
-Peptide Aggregation by Physiological
Concentrations of Calcium

http://www.utdallas.edu/~tres/papers/isaacs.2006.pdf


Real-Time Monitoring of Apoptosis by Caspase-3-Like Protease
Induced FRET Reduction Triggered by Amyloid Aggregation

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2426809



Unfortunately, it still seems to be too early in the amyloid research to guess which of the amyloid-related diseases will be helped by breaking up the amyloids, and which will be made worse or stay about the same.

Some news on nattokinase, known to break up amyloid fibrils.
Extracted from natto, a fermented soy food.


Amyloid-degrading ability of nattokinase from Bacillus subtilis natto.
http://www.ncbi.nlm.nih.gov/pubmed/19117402?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum


Natto and Alzheimer's disease
http://www.aocs.org/news/story.cfm?id=884


Eat Natto and Care for Your Cardiovascular System Naturally
http://www.naturalnews.com/025684.html


Natto enzyme may reduce Alzheimer’s risk: Study
http://www.nutraingredients-usa.com/Publications/Food-Beverage-Nutrition/NutraIngredients.com/Research/Natto-enzyme-may-reduce-Alzheimer-s-risk-Study


Nattokinase Enzyme Reduces Alzheimer's Risk: Health Blog
http://www.jonbarron.org/blog_published/2009/02/nattokinase_enzyme_reduces_alz.html


Soybean product fights abnormal protein involved in Alzheimer's disease
http://www.sciencecentric.com/news/article.php?q=09021943-soybean-product-fights-abnormal-protein-involved-alzheimer-disease


Soybean Product Fights Abnormal Protein Involved In Alzheimer’s Disease
http://www.sciencedaily.com/releases/2009/02/090218223842.htm


Soybean-derived enzyme (nattokinase) busts Alzheimer's-type amyloid plaques
http://www.prohealth.com/library/showarticle.cfm?LIBID=14340

Another amyloid breaker - proteinase K. This one has been investigated in connection with with prion diseases and Alzheimer's.


Formation of Soluble Oligomers and Amyloid Fibrils with Physical Properties of the Scrapie Isoform of the Prion Protein from the C-terminal Domain of Recombinant Murine Prion Protein mPrP-(121–231)
http://www.jbc.org/cgi/content/abstract/281/36/26121


Common new amyloid
http://www.mad-cow.org/jul99_late_sci.html


Evaluation of Quinacrine Treatment for Prion Diseases
http://jvi.asm.org/cgi/content/abstract/77/15/8462


Transmissibility of mouse AApoAII amyloid fibrils: inactivation by physical and chemical methods
http://www.fasebj.org/cgi/content/full/20/7/1012


The [URE3] Yeast Prion Results from Protein Aggregates That Differ from Amyloid Filaments Formed in Vitro
http://www.jbc.org/cgi/content/abstract/279/49/50962


Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease
http://www.ncbi.nlm.nih.gov/pubmed/2900137


Prions
http://www.mad-cow.org/nov97_sci.html


SMART: A4_EXTRA domain annotation
http://smart.embl-heidelberg.de/smart/do_annotation.pl?BLAST=DUMMY&DOMAIN=SM00006


8. Methods for Conversion of Prion Protein into Amyloid Fibrils
http://www.springerprotocols.com/Abstract/doi/10.1007/978-1-59745-234-2_8

Some news on nattokinase, known to break up amyloid fibrils.
Extracted from natto, a fermented soy food.

The good thing about nattokinase is that it's safe, at least in the doses obtained from eating natto, since it's a food that's been eaten for years. The vitamin K2 (MK7) it contains has been shown to reduce the rate of fractures in the elderly.

StephenB

---

Some news on nattokinase, known to break up amyloid fibrils.
Extracted from natto, a fermented soy food.

The good thing about nattokinase is that it's safe, at least in the doses obtained from eating natto, since it's a food that's been eaten for years. The vitamin K2 (MK7) it contains has been shown to reduce the rate of fractures in the elderly.

StephenB

Not likely that nattokinase go directly to the blood after you ate natto. And that would be the point of a drug. So not granted it will be safe, plus you might need to take it intravenously, as many other drugs that are broken down by stomach chemistry.

A4_EXTRA - amyloid A4 precursor of Alzheimers disease

http://smart.embl-heidelberg.de/smart/do_annotation.pl?BLAST=DUMMY&DOMAIN=SM00006>

Some information about a protein associated with
Alzheimer's. When it breaks down the wrong way,
one of the products is the amyloids associated
with Alzheimer's.

So far I've found the names of two substances said to interfere with amyloid formation:

phenol red
nattokinase

My brother was recently cured of ameloidosis formation with interferon (T-Cell?) treatments at OHSU in Portland, OR
On the down side, it was not before it destroyed his kidney function. I guess the little buggers cause problems for many different organs. He is now on dialysis, as, sadly, so am I, due to having only one kidney, and long term high blood pressure. Go figure.

Lloyd M Johnston
lloydmj@starband.net

---

Clioquinol and Alzheimer's

Some research indicates that an old drug named clioquinol may help Alzheimer's, possibly by reducing the number of metal ions that can bind to amyloids.

Researchers don't agree on which metals are involved, although aluminum seems likely.


'...and C is for Clioquinol' - the AbetaCs of Alzheimer's disease.

http://www.ncbi.nlm.nih.gov/pubmed/11852134?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=2&log$=relatedreviews&logdbfrom=pubmed


Aluminum and other metals in Alzheimer's disease: a review of potential therapy with chelating agents.

http://www.ncbi.nlm.nih.gov/pubmed/17119296?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=5&log$=relatedreviews&logdbfrom=pubmed


Alzforum: Drugs In Clinical Trials - Clioquinol

http://www.alzforum.org/drg/drc/detail.asp?id=93


Alzheimer's Reading Room: Can Clioquinol Stop Alzheimer's?

http://www.alzheimersreadingroom.com/2009/01/can-clioquinol-stop-alzheimers.html


Alzheimer's Weekly: Clioquinol May Alleviate Alzheimer's

http://www.alzheimersweekly.com/Research/clioquinol-may-alleviate-alzheimers-a432.html


Clioquinol - Wikipedia, the free encyclopedia

http://en.wikipedia.org/wiki/Clioquinol


Clioquinol for the treatment of Alzheimer's Disease.

http://www.ncbi.nlm.nih.gov/pubmed/16437529



Clioquinol helps the R6/2 mouse

http://www.hdlighthouse.org/research/drugs-supps/updates/1383clioquinol.php


Clioquinol mediates copper uptake and counteracts copper efflux activities of the amyloid precursor protein of Alzheimer's disease.

http://www.ncbi.nlm.nih.gov/pubmed/15465814?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=2&log$=relatedarticles&logdbfrom=pubmed


Clinical trial of Alzheimer's disease drug shows clear reductions in AD development

http://www.seniorjournal.com/NEWS/Alzheimer's/3-12-16cloquinol.htm


Copper and clioquinol treatment in young APP transgenic and wild-type mice: effects on life expectancy, body weight, and metal-ion levels.

http://www.ncbi.nlm.nih.gov/pubmed/17211610?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=1&log$=relatedarticles&logdbfrom=pubmed


Radioiodinated clioquinol as a biomarker for beta-amyloid: Zn complexes in Alzheimer's disease.

http://www.ncbi.nlm.nih.gov/pubmed/16441845?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=1&log$=relatedarticles&logdbfrom=pubmed


Phase 1-2 Study of Clioquinol in Alzheimer's Disease

http://www.jefferson.edu/fin/patients/clioquinol.cfm


Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice.

http://www.ncbi.nlm.nih.gov/pubmed/11430801?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=1&log$=relatedarticles&logdbfrom=pubmed



However, I didn't see any research papers on this dated later than 2007.

Aluminum and Alzheimer's


Aluminium in Alzheimer's disease: are we still at a crossroad?

http://www.ncbi.nlm.nih.gov/pubmed/15666086?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=3&log$=relatedreviews&logdbfrom=pubmed


Aluminum and Alzheimer's disease: a new look.

http://www.ncbi.nlm.nih.gov/pubmed/17119287?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=5&log$=relatedreviews&logdbfrom=pubmed


Aluminum and other metals in Alzheimer's disease: a review of potential therapy with chelating agents.

http://www.ncbi.nlm.nih.gov/pubmed/17119296?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=5&log$=relatedreviews&logdbfrom=pubmed


Aluminum modifies the properties of Alzheimer's disease PHF tau proteins in vivo and in vitro.

http://www.ncbi.nlm.nih.gov/pubmed/7525898?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=1&log$=relatedarticles&logdbfrom=pubmed


Aluminum modulates effects of beta amyloid(1-42) on neuronal calcium homeostasis and mitochondria functioning and is altered in a triple transgenic mouse model of Alzheimer's disease.

http://www.ncbi.nlm.nih.gov/pubmed/18788899?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=2&log$=relatedarticles&logdbfrom=pubmed


An aluminum-based rat model for Alzheimer's disease exhibits oxidative damage, inhibition of PP2A activity, hyperphosphorylated tau, and granulovacuolar degeneration.

http://www.ncbi.nlm.nih.gov/pubmed/17662457?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=3&log$=relatedarticles&logdbfrom=pubmed


Can the controversy of the role of aluminum in Alzheimer's disease be resolved? What are the suggested approaches to this controversy and methodological issues to be considered?

http://www.ncbi.nlm.nih.gov/pubmed/8772802?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=5&log$=relatedreviews&logdbfrom=pubmed


Effects of aluminum on the nervous system and its possible link with neurodegenerative diseases.

http://www.ncbi.nlm.nih.gov/pubmed/16308486?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=2&log$=relatedreviews&logdbfrom=pubmed


Interaction of aluminum with paired helical filament tau is involved in neurofibrillary pathology of Alzheimer's disease.

http://www.ncbi.nlm.nih.gov/pubmed/9187935?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=3&log$=relatedreviews&logdbfrom=pubmed


Reversal by desferrioxamine of tau protein aggregates following two days of treatment in aluminum-induced neurofibrillary degeneration in rabbit: implications for clinical trials in Alzheimer's disease.

http://www.ncbi.nlm.nih.gov/pubmed/9187935?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=3&log$=relatedreviews&logdbfrom=pubmed


The role of metals in the etiology of Alzheimer's disease.

http://www.ncbi.nlm.nih.gov/pubmed/17522444?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=3&log$=relatedreviews&logdbfrom=pubmed

Other metals and Alzheimer's


Some research reports on metals, but not specific metals, involved in amyloid formation in Alzheimer's:


Amyloid-beta metal interaction and metal chelation.

http://www.ncbi.nlm.nih.gov/pubmed/15709482?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=2&log$=relatedreviews&logdbfrom=pubmed


Metal chelator decreases Alzheimer beta-amyloid plaques.

http://www.ncbi.nlm.nih.gov/pubmed/11430794?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=5&log$=relatedreviews&logdbfrom=pubmed


The role of metals in the etiology of Alzheimer's disease.

http://www.ncbi.nlm.nih.gov/pubmed/17522444?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=4&log$=relatedreviews&logdbfrom=pubmed


Transition metal chelator therapy--a potential treatment for Alzheimer's disease?

http://www.ncbi.nlm.nih.gov/pubmed/11897554?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=5&log$=relatedreviews&logdbfrom=pubmed

Other chelators and Alzheimer's


Some other chelators have also been tested for controlling the metals involved in Alzheimer's:


Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta.

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=18614028



The lipophilic metal chelator DP-109 reduces amyloid pathology in brains of human beta-amyloid precursor protein transgenic mice.

http://www.ncbi.nlm.nih.gov/pubmed/15465629?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=4&log$=relatedarticles&logdbfrom=pubmed

Some research into a possible toxic agent for Alzheimer's, related to the amyloids:

Alzheimer's Research Yields Potential Drug Target

http://www.medicalnewstoday.com/articles/156430.php

It seems that amyloid beta 42 peptides combine into dodecamers (groups of 12 molecules bound to each other), and these dodecamers are likely to be the toxic agent.

Can minirosetta handle dodecamers of that peptide? If not, is adding this capability planned?