Understanding Prions In Neurodegenerative Diseases

Priyanka Saha, Amity University Kolkata

Introduction to prions

Prions are infectious-disease causing agents which are mainly bits of misshapen proteins, more precisely referred to as “proteinaceous infectious particles”. After entering any living body, it misshapes the other proteins by deforming them during a sequence reaction until the brain is stuffed with holes like ‘Cheese’. Prions do not seem to be living just like the bacteria or parasite, hence there is not any possible way to ‘kill’ them and persists within the environment for years and may also additionally survive normal sterilization techniques. They normally enter any living body through contaminated food or medical equipment or are often inherited from the family and cause neurological disorders and prion diseases.

Disorders related to CNS – Neurodegenerative diseases 

Neurodegenerative diseases are the disorders that involve the death of certain brain parts which are incurable and fatal that consists of an outsized range of illnesses, like Alzheimer’s disease (Aβ and tau) and other dementias, Parkinson’s disease (α-synuclein), Huntington’s disease, Efferent Neuron Disease, and Prion disease (Prion protein). They’re mainly associated with the intracellular or extracellular accumulation of misshaped protein within the brain. These abnormal protein deposits cause the dysfunction and subsequent loss of neurons in the CNS. As a result, there arises an oversized range of clinical symptoms like cognitive decline, dementia, and gradual loss of locomotory functions. Neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease are increasingly stated as “prion-like” disorders.

Diagnosis of Prion diseases 

Prion diseases mainly affect the brain tissues and cells hence, taking a sample from brain tissue during a biopsy or after death can diagnose it. Healthcare providers do sort of tests before to help diagnose prion diseases like Creutzfeldt-Jakob disease (CJD) or to rule out other diseases with similar symptoms.

The tests include:

• MRI (Magnetic Resonance Imaging) of the brain

• Samples of fluids from the spinal cord (Lumbar Puncture)

• Electroencephalogram, which analyses brain waves

• Blood tests 

• Neurologic and visual exams to examine nerve damage and eyesight difficulty

Prion diseases are a scarce form of neurodegenerative disorders 

Prion diseases are a rare group of neurodegenerative diseases that happens in animals additionally as in humans. Prion diseases occur, when normal prion proteins, found on the surface of various cells, become abnormal and clump within the brain, causing brain damage. The excessive accumulation of prions within the brain has a lot of disadvantages which include loss of memory, change in behavior, and trouble with movement. Here a misshaped form of an endogenous protein, prion protein (PrPC), interacts to make β-sheet rich structures with the propensity to aggregate within the CNS. The misfolded prion protein, termed prion (PrPSc), forms a template that converts further PrPC monomers into the abnormal and disease-associated isoform. Familiar kinds of Prion diseases are CJD in humans, Scrapie disease in sheeps and goats, Bovine spongiform encephalopathy (BSE) in cattle, Mad cow disease in cows, Chronic wasting disease (CWD) in deers, etc. The symptoms include hallucinations, muscle stiffness, fatigue, rapidly developing dementia, difficulty in walking, changes in gait, and difficulty in talking.

Communicability of Prion diseases

Human prion diseases are rare, but their transmissibility, lengthy incubation periods, and resistance to standard decontamination methods pose a substantial risk to public health. The first human prion disease that transmitted between humans is called ‘Kuru’. However, the spread of this disease from one person to another is quite restricted because it has lesser modes of transmission, amongst which the main mode of transmission is from decaying brain cells and tissues of the deceased during funerals. The primary transmission mode in a case of CJD was when a patient received a transplant from a donor who died of the same disease. In several CJD transmission cases, it has been observed that the patients were operated on with contaminated neurosurgical instruments or stereotactic electroencephalogram electrodes. The maximum number of Iatrogenic Creutzfeldt Jakob Disease (iCJD) cases arose in patients who got contaminated with hormones like human growth hormone or human gonadotropin hormones. And also during transplantation like human dura mater (HDM) grafts. To control such cases, all other pituitary hormones were immediately stopped from getting secreted and replaced with recombinant pituitary hormones. Cases of secondary varied CJD occurred in patients who received transfusions with non-leuko-depleted red cell concentrates from asymptomatic donors that would go on to develop the same disease, later on. For the blood recipients, the resting period is between 7-9 years and 1-3 years for donors. In 2004, a patient died from a non-neurological disorder (from an accumulation of prions within the spleen and cervical lymphoid tissue, not in the brain) after five years of receiving a red cell transfusion from a donor who developed Variant Creutzfeldt-Jakob Disease (vCJD). Diseases caused by prions are therefore communicable even after being silenced for a long period in a living body.

Possible treatments for Prion diseases

For now, there is no promising treatment for treating prion diseases, let alone cures. However, this can be controlled by some supportive treatments like:

1) Preliminary medications: Some medications help in treating some basic symptoms like:

1. Sedatives or antidepressants for controlling psychological problems
2. Sodium valproate and clonazepam for easing muscle pain, anxiety, and seizures
3. Opioid medication for pain relief including anesthesia

2) Adequate amount of nutrients: A balanced diet with a lot of essential nutrients is mandatory to take in to aid in better functioning of the immune system. Supplements are also necessary to consume.

3) Intravenous Fluid Regulation: In dire situations, IV fluids and feeding tubes become necessary to assist the patient.

4) Anti-prion antibodies: These are naturally or artificially occurring antibodies that are being used to treat prion diseases. Humans can make their antibodies for nascent prion infection. The lack of such antibodies in disease carriers related to PRNP mutation suggests a connection to low cases of spontaneous prion diseases in humans.   However, antibodies for mutant prion genes are still under research.

Prevention is better than cure

Prion diseases can not be cured fully, it is recommended by medical supervisors to take proper prevention to avoid such type of deadly disease.

Some of the preventive steps include:

1. Interdicting use of body parts such as the brain and spinal cord, especially of the cow for food purposes.
2. Use of sterilization practice on surgical equipment that has potentially come in contact with the CNS or nervous tissue of someone having suspected prion disease.
3. Preventing people who have a past or risk for vulnerability to prion diseases from blood donations or other organs and tissues.
4. Timely disposing of the disposable medical pieces of equipment.
5. Stricter rules for importing cattle from places having mad cow disease.
6. For those that inherited prion diseases, taking proper medical advice and regular checkups will be beneficial.

Conclusion

Prion diseases are an extremely rare form of neurodegenerative disease and are caused by abnormal misshaped proteins in the brain. Such diseases can be either be inherited genetically or more likely, can enter the body from contaminated food and medical instruments. Although there is no cure for prion diseases yet,  preliminary aid comprising medications suppress pain and ease symptoms. A lot of researchers are trying to discover potential treatments or drugs for treating prion diseases effectively, and further reports on that aspect are deemed necessary.

Also read: Analysis of the interaction sites of SARS-CoV-2

REFERENCES :

1. Walker, L., McAleese, K.E., Erskine, D., Attems, J.,(2019). Neurodegenerative Diseases and Ageing. Subcell. Biochem. 91, 75–106. https://doi.org/10.3390/biom11020207
2. Soto, C.; Pritzkow, (2018), Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases. Nat. Neurosci, 21, 1332–1340. https://doi.org/10.3390/biom11020207
3. Dawson TM, Golde TE, Lagier-Tourenne C (2018) Animal models of neurodegenerative diseases. Nat Neurosci 21(10):1370–1379. https://doi.org/10.1186/s40478-021-01123-8
4. Prusiner SB (2013). Biology and genetics of prions causing neurodegeneration. Annual review of genetics, 47, 601-23. https://doi.org/10.1126/science.1222951

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