Hey Steemians,

Today I was going through some of the research articles on viruses and prions. There I found an article mentioning about good side of prions. The moment we hear about viruses and prions the first thing which comes to our mind is diseases they cause and how much devastating they can be but it has been shown that these prions have a good side also, as it is said there is always two sides of coins so do prions have good side and bad side. Before going into the explanation of good properties of prions let me first give an introduction about prions.

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Prions are infectious agents which are entirely made up of proteins which are misfolded. Prions are made up of prion protein (PrP) (1). Two researchers from London Tikvah Alper and John Stanley Griffith in 1960s were first to make hypothesis about prions as causative agent of transmissible spongiform encephalopathies- a condition which affects the brain and nervous system of many animals including humans (2). In 1982 Stanley Prusiner from University of California made an announcement regarding purification of prion in his lab. For his work in prions he was awarded with Nobel Prize in Physiology or Medicine in 1997 (3).

Before starting to the structure of prions I will just name some of the diseases which are caused by prions. Scrapie (Sheep), Bovine spongiform encephalopathy commonly known as mad cow disease (cattle), Kuru (human), Creutzfeldt-Jakob disease (CJD in human), feline spongiform encephalopathy (cat) (4).

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Prion Protein (PrP) - there are two types of them one is normal prion PrPC(c stands for cellular) and other is infectious prion PrPSc (Sc stand for scrapie a prion disease which occurs in sheep). The cellular prion that is PrPC are mainly alpha helical in structure contributing 42% and two beta sheets covers 3% of the structure. The alpha helix is connected to the beta sheets by disulfide bridges. They vary in their molecular weight from 30-35 kDa due to dependence on the glycosylation at two asparagine residues near C-terminus (5). PrP remain bound to the membrane by glycolipid which can be digested by enzyme phosphoinositide phospholipase C which acts on glycolipid anchor that is glycophosphatidylinositol (6). PrPSc is infectious form which always causes disease. In contrast to PrPC, its structure is mainly composed of beta sheets (54%). PrPSc can convert cellular form of prion into infectious form and it aggregates into highly structured amyloid fibers (7).

To understand replication in prion which is totally protein based two models were proposed one is heterodimer model of propagation and other is fibril model of propagation. In heterodimer model, PrPSc binds with the PrPC and induces conformational changes which results in conversion of it into PrPSc, after this they separate and carry out conversion of other normal PrP into infectious PrPSc (8). The other model is fibril model assumed that PrPSc are fibrils and their ends interact with PrPC and convert them to PrPSc (9). The transmission of prion can occur in three ways; sporadic, familial or acquired. The one of transmission is conversion of PrPC into PrPSc. Some researchers have shown that prion disease can be acquired by ingestion of prions as they get deposited in environment from the remains of dead animals, urine, and saliva (10).

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The prions are known for aggregating and this aggregating nature that is formation of amyloids which are documented in patients suffering from neurodegenerative diseases. The prion like domain paly role in aggregation of proteins and further complication. It has been shown that TDP-43, an RNA binding domain whose aggregation leads to motor neuron disease (death of motor neuron) is aggregated by prion like domains (11). The other diseases which are caused by amyloid formation through prion like domains are Huntington’s disease and Alzheimer’s disease (12).

Now talk about the good side of these prions. The cellular or non-infectious form prion PrPC is predominant in the synaptic localization from where point one nerve passes signal to other nerve which suggests that it plays an important signaling. PrPC also shows high expression in immature brain which may play a role in neurogenesis during childhood (13). Scientists have found that hematopoietic stem cells express PrP which plays a role in stem cell renewal same study they carry out in hematopoietic stem cell which lacks PrP these stem cells were more sensitive to cell depletion in comparison to one with PrP (14).

Cellular form of these PrPC are transported to the cell membrane by glycosylphosphatidylinositol anchor. These prion proteins are expressed almost in all tissue and mostly in brain.

In this study, PrPC deficient (Prnp) mice were used to confirm whether the prion protein are involved or not in the synaptic plasticity process in neonatal hippocampus. The whole study by the Cherubini group suggested that the lack of expression of PrPC is the cause of activity-dependent modifications and the gating role of PKA-signaling in the regulation of synaptic plasticity and the developmental studies of hippocampus.

So, these prion protein (PrPC) have a crucial role in the developmental stages of hippocampus, by regulating the synaptic plasticity. 

Along with this, prion proteins are also playing a crucial role in the self-renewal of the stem cells -A study by the Harvey Lodish group. 

Flow cytometry analysis shows that the  LT HSCs (Long-Term Hematopoietic stem cells) were expressed on the surface of bone marrow. And the positive and negative fractions of these populations, followed by the reconstitution assay, shows that LT HSCs expresses PrP.

Suggesting PrP is a marker for the stem cells and helps them in their self renewal.

Summary

Despite of being infectious and deadly proteinacious material, causing disease and infecting animals worldwide they have a good side also. Where they play crucial role in the developmental stage of neonatal hippocampus and are expressed and known to play a role in providing the stem cell self-renewal capacity. Proving that everything has a bright side of it also, you just need the vision to see it.

Video Source

Prions: Incurable Brain Dissolving Protein

Reference

Prusiner et. al., 1991 Molecular biology of prion diseases. 252(5012),1515-1522. 

Alper et. al., 1967 Does the Agent of Scrapie Replicate without Nucleic Acid? 214,764-766.

The Nobel Prize in Physiology or Medicine 1997.

Prion (Wikipedia)

Riek et. al., 1996 NMR structure of the mouse prion protein domain PrP(121–231). 382,180-182.

Weissmann et. al., 2004 The state of the prion. 2(11),861-871.

Pan et. al., 1993 Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins. 90(23),10962-10966.

Cohen et. al., 1994 Structural clues to prion replication. 264(5158),530-531.

Beekes et. al., 1996 Sequential appearance and accumulation of pathognomonic markers in the central nervous system of hamsters orally infected with scrapie. 77,1925-1934.

Johnson et. al., 2007 Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles. 3(7).

King et. al., 2012 The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease. 1462,61-80.

David et. al., 2012 The Amyloid State of Proteins in Human Diseases.148(6),1188-1203.

Caiati et. al., 2013 PrPC Controls via Protein Kinase A the Direction of Synaptic Plasticity in the Immature Hippocampus. 33(7),2973-2983.

Zhang et. al., 2006 Prion protein is expressed on long-term repopulating hematopoietic stem cells and is important for their self-renewal. 103(7),2184-2189.

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