Infected water from animal manure, prion disease and Parkinson

Prion diseases and their transmission properties

Diseases caused by prions
Affected animal(s) Disease
sheepgoat Scrapie[43]
cattle Bovine spongiform encephalopathy (BSE), mad cow disease[43]
mink[43] Transmissible mink encephalopathy (TME)
white-tailed deer, elk, mule deer, moose[43] Chronic wasting disease (CWD)
cat[43] Feline spongiform encephalopathy (FSE)
nyalaoryxgreater kudu[43] Exotic ungulate encephalopathy (EUE)
ostrich[44] Spongiform encephalopathy
(Has not been shown to be transmissible.)
human Creutzfeldt–Jakob disease (CJD)[43]
Iatrogenic Creutzfeldt–Jakob disease (iCJD)
Variant Creutzfeldt–Jakob disease (vCJD)
Familial Creutzfeldt–Jakob disease (fCJD)
Sporadic Creutzfeldt–Jakob disease (sCJD)
Gerstmann–Sträussler–Scheinker syndrome (GSS)[43]
Fatal familial insomnia (FFI)[45]
Familial spongiform encephalopathy[46]
Multiple System Atrophy (MSA): Not a TSE and is not by typical prions Prp/PrPSc but by a misfolded α-Synuclein.[47]

Until 2015 all known mammalian prion diseases were considered to be caused by the prion protein, PrP; in 2015 Multiple System Atrophy was found to be likely caused by a new prion, the misfolded form of a protein called alpha-synuclein.[4]The endogenous, properly folded form of the prion protein is denoted PrPC (for Common or Cellular), whereas the disease-linked, misfolded form is denoted PrPSc (for Scrapie), after one of the diseases first linked to prions and neurodegeneration.)[22][48] The precise structure of the prion is not known, though they can be formed by combining PrPC, polyadenylic acid, and lipids in a protein misfolding cyclic amplification (PMCA) reaction.[49] Proteins showing prion-type behavior are also found in some fungi, which has been useful in helping to understand mammalian prions. Fungal prions do not appear to cause disease in their hosts.[50]

Prions cause neurodegenerative disease by aggregating extracellularly within the central nervous system to form plaques known as amyloid, which disrupt the normal tissue structure. This disruption is characterized by “holes” in the tissue with resultant spongy architecture due to the vacuole formation in the neurons.[51]Other histological changes include astrogliosis and the absence of an inflammatory reaction.[52] While the incubation period for prion diseases is relatively long (5 to 20 years), once symptoms appear the disease progresses rapidly, leading to brain damage and death.[53] Neurodegenerative symptoms can include convulsionsdementiaataxia (balance and coordination dysfunction), and behavioural or personality changes.

All known prion diseases, collectively called transmissible spongiform encephalopathies (TSEs), are untreatable and fatal.[54] However, a vaccine developed in mice may provide insight into providing a vaccine to resist prion infections in humans.[55] Additionally, in 2006 scientists announced that they had genetically engineered cattle lacking a necessary gene for prion production – thus theoretically making them immune to BSE,[56] building on research indicating that mice lacking normally occurring prion protein are resistant to infection by scrapie prion protein.[57] In 2013, a study revealed that 1 in 2,000 people in the United Kingdom might harbour the infectious prion protein that causes vCJD.[58]

Many different mammalian species can be affected by prion diseases, as the prion protein (PrP) is very similar in all mammals.[59] Due to small differences in PrP between different species it is unusual for a prion disease to transmit from one species to another. The human prion disease variant Creutzfeldt–Jakob disease, however, is believed to be caused by a prion that typically infects cattle, causing Bovine spongiform encephalopathy and is transmitted through infected meat.[60]


It has been recognized that prion diseases can arise in three different ways: acquired, familial, or sporadic.[61] It is often assumed that the diseased form directly interacts with the normal form to make it rearrange its structure. One idea, the “Protein X” hypothesis, is that an as-yet unidentified cellular protein (Protein X) enables the conversion of PrPC to PrPSc by bringing a molecule of each of the two together into a complex.[62]

Current research suggests that the primary method of infection in animals is through ingestion. It is thought that prions may be deposited in the environment through the remains of dead animals and via urine, saliva, and other body fluids. They may then linger in the soil by binding to clay and other minerals.[63]

A University of California research team, led by Nobel Prize winner Stanley Prusiner, has provided evidence for the theory that infection can occur from prions in manure.[64] And, since manure is present in many areas surrounding water reservoirs, as well as used on many crop fields, it raises the possibility of widespread transmission. It was reported in January 2011 that researchers had discovered prions spreading through airborne transmission on aerosol particles, in an animal testingexperiment focusing on scrapie infection in laboratory mice.[65] Preliminary evidence supporting the notion that prions can be transmitted through use of urine-derived human menopausal gonadotropin, administered for the treatment of infertility, was published in 2011.[66]

Prions in plants

In 2015, researchers at The University of Texas Health Science Center at Houston found that plants can be a vector for prions. When researchers fed hamsters grass that grew on ground where a deer that died with chronic wasting disease (CWD) was buried, the hamsters became ill with CWD, suggesting that prions can bind to plants, which then take them up into the leaf and stem structure, where they can be eaten by herbivores, thus completing the cycle. It is thus possible that there is a progressively accumulating number of prions in the environment.[67][68]


Infectious particles possessing nucleic acid are dependent upon it to direct their continued replication. Prions, however, are infectious by their effect on normal versions of the protein. Sterilizing prions, therefore, requires the denaturation of the protein to a state in which the molecule is no longer able to induce the abnormal folding of normal proteins. In general, prions are quite resistant to proteases, heat, ionizing radiation, and formaldehyde treatments,[69] although their infectivity can be reduced by such treatments. Effective prion decontamination relies upon protein hydrolysis or reduction or destruction of protein tertiary structure. Examples include sodium hypochloritesodium hydroxide, and strongly acidic detergents such as LpH.[70] 134 °C (274 °F) for 18 minutes in a pressurized steam autoclave has been found to be somewhat effective in deactivating the agent of disease.[71][72] Ozone sterilization is currently being studied as a potential method for prion denaturation and deactivation.[73] Renaturation of a completely denatured prion to infectious status has not yet been achieved; however, partially denatured prions can be renatured to an infective status under certain artificial conditions.[74]

The World Health Organization recommends any of the following three procedures for the sterilization of all heat-resistant surgical instruments to ensure that they are not contaminated with prions:

  1. Immerse in 1N sodium hydroxide and place in a gravity-displacement autoclave at 121 °C for 30 minutes; clean; rinse in water; and then perform routine sterilization processes.
  2. Immerse in 1N sodium hypochlorite (20,000 parts per million available chlorine) for 1 hour; transfer instruments to water; heat in a gravity-displacement autoclave at 121 °C for 1 hour; clean; and then perform routine sterilization processes.
  3. Immerse in 1N sodium hydroxide or sodium hypochlorite (20,000 parts per million available chlorine) for 1 hour; remove and rinse in water, then transfer to an open pan and heat in a gravity-displacement (121 °C) or in a porous-load (134 °C) autoclave for 1 hour; clean; and then perform routine sterilization processes.[75]

Prion-like domains

While PrP is considered the only mammalian prion, prion-like domains have been found in a variety of other mammalian proteins. Some of these proteins have been implicated in the ontogeny of age-related neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS, known as Motor Neurone Disease outside the US), frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U), Alzheimer’s disease, and Huntington’s disease,[76] as well as some forms of Systemic Amyloidosis including AA (Secondary) Amyloidosis that develops in humans and animals with inflammatory and infectious diseases such as TuberculosisCrohn’s diseaseRheumatoid arthritis, and HIV AIDSAA amyloidosis, like prion disease, may be transmissible.[77] This has given rise to the ‘prion paradigm’, where otherwise harmless proteins can be converted to a pathogenic form by a small number of misfolded, nucleating proteins.[78]

The definition of a prion-like domain arises from the study of fungal prions. In yeast, prionogenic proteins have a portable prion domain that is both necessary and sufficient for self-templating and protein aggregation. This has been shown by attaching the prion domain to a reporter protein, which then aggregates like a known prion. Similarly, removing the prion domain from a fungal prion protein inhibits prionogenesis. This modular view of prion behaviour has led to the hypothesis that similar prion domains are present in animal proteins, in addition to PrP.[76] These fungal prion domains have several characteristic sequence features. They are typically enriched in asparagine, glutamine, tyrosine and glycine residues, with an asparagine bias being particularly conducive to the aggregative property of prions. Historically, prionogenesis has been seen as independent of sequence and only dependent on relative residue content. However, this has been shown to be false, with the spacing of prolines and charged residues having been shown to be critical in amyloid formation.[5]

Bioinformatic screens have predicted that over 250 human proteins contain prion-like domains (PrLD). These domains are hypothesized to have the same transmissible, amyloidogenic properties of PrP and known fungal proteins. As in yeast, proteins involved in gene expression and RNA binding seem to be particularly enriched in PrLD’s, compared to other classes of protein. In particular, 29 of the known 210 proteins with an RNA recognition motif also have a putative prion domain. Meanwhile, several of these RNA-binding proteins have been independently identified as pathogenic in cases of ALS, FTLD-U, Alzheimer’s disease, and Huntington’s disease.[79]

Role in neurodegenerative disease

The pathogenicity of prions and proteins with prion-like domains arises from their self-templating ability and the resulting exponential growth of amyloid fibrils. The presence of amyloid fibrils in patients with degenerative diseases has been well documented. These amyloid fibrils are seen as the result of pathogenic proteins that self-propagate and form highly stable, non-functional aggregates.[79] While this does not necessarily imply a causal relationship between amyloid and degenerative diseases, the toxicity of certain amyloid forms and the overproduction of amyloid in familial cases of degenerative disorders supports the idea that amyloid formation is generally toxic.

Specifically, aggregation of TDP-43, an RNA-binding protein, has been found in ALS/MND patients, and mutations in the genes coding for these proteins have been identified in familial cases of ALS/MND. These mutations promote the misfolding of the proteins into a prion-like conformation. The misfolded form of TDP-43 forms cytoplasmic inclusions in afflicted neurons, and is found depleted in the nucleus. In addition to ALS/MND and FTLD-U, TDP-43 pathology is a feature of many cases of Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. The misfolding of TDP-43 is largely directed by its prion-like domain. This domain is inherently prone to misfolding, while pathological mutations in TDP-43 have been found to increase this propensity to misfold, explaining the presence of these mutations in familial cases of ALS/MND. As in yeast, the prion-like domain of TDP-43 has been shown to be both necessary and sufficient for protein misfolding and aggregation.[76]

Similarly, pathogenic mutations have been identified in the prion-like domains of heterogeneous nuclear riboproteins hnRNPA2B1 and hnRNPA1 in familial cases of muscle, brain, bone and motor neuron degeneration. The wild-type form of all of these proteins show a tendency to self-assemble into amyloid fibrils, while the pathogenic mutations exacerbate this behaviour and lead to excess accumulation.[80]


Fungal proteins exhibiting templated conformational change were discovered in the yeast Saccharomyces cerevisiae by Reed Wickner in the early 1990s. For their mechanistic similarity to mammalian prions, they were termed yeast prions. Subsequent to this, a prion has also been found in the fungus Podospora anserina. These prions behave similarly to PrP, but, in general, are nontoxic to their hosts. Susan Lindquist‘s group at the Whitehead Institute has argued some of the fungal prions are not associated with any disease state, but may have a useful role; however, researchers at the NIH have also provided arguments suggesting that fungal prions could be considered a diseased state.[81] There is mounting evidence that fungal proteins have evolved specific functions that are beneficial to the microorganism that enhance their ability to adapt to their diverse environments.[82]

As of 2012, there are eight known prion proteins in fungi, seven in Saccharomyces cerevisiae (Sup35, Rnq1, Ure2, Swi1, Mot3, Cyc8, and Mod5) and one in Podospora anserina (HET-s).[contradictory] The article that reported the discovery of a prion form, the Mca1 protein, was retracted due to the fact that the data could not be reproduced.[83] Notably, most of the fungal prions are based on glutamine/asparagine-rich sequences, with the exception of HET-s and Mod5.

Research into fungal prions has given strong support to the protein-only concept, since purified protein extracted from cells with a prion state has been demonstrated to convert the normal form of the protein into a misfolded form in vitro, and in the process, preserve the information corresponding to different strains of the prion state. It has also shed some light on prion domains, which are regions in a protein that promote the conversion into a prion. Fungal prions have helped to suggest mechanisms of conversion that may apply to all prions, though fungal prions appear distinct from infectious mammalian prions in the lack of cofactor required for propagation. The characteristic prion domains may vary between species—e.g., characteristic fungal prion domains are not found in mammalian prions.

Connie’s comments: I have a client with Parkinson, Dementia and Lew Body diseases who likes to drink raw milk. Do drink pasteurized milk and milk products. I do not drink milk.


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