prions,types, disease, prevention and treatment

Pirons

1. PRIONS: Presented by : ABDUL REHMAN Presented to : DR. AQSA Department: MMG

2. Prions (Definition): The term Prion means proteinaceous infectious particles. Prions are the infectious agents responsible for several neurodegenerative diseases in mammals, like, Creutzfeldt Jacob disease. This happens due to the abnormal folding of the proteins in the brain. It refers to the hypothesis that the infectious agents causing the diseases contain only proteins. It explained why the infectious agents are resistant to ultraviolet radiations. They can break down the nucleic acids, but are receptive to substances that denature proteins.

3. Structure and Replication: Abnormal shape No nucleic acid Proteinaceous infections particle Normal and Aberrant Forms Molecular Models Cell Biology Key structural elements

4. Types of Prions: Creutzfeldt Jacob Disease Variant (CJD) Variably protease sensitive prionopathy (VPSPr) Gerstmann-Straussler-Scheinker disease (GSS) Kuru Fatal insomnia (FI)

5. Prions diseases Creutzfeldt Jacob Disease: Creutzfeldt Jacob Disease is rare rapidly worsening brain disorder that causes unique change in brain tissues and affects muscle coordination thinking and memory.

6. History and discovery: The disease was first described in the 1920s by the German neurologists Hans Gerhard Creutzfeldt and Alfons Maria Jacob. CJD is similar to other neurodegenerative diseases such as  Kuru , a human disorder, and  scrapie , which occurs in sheep and goats. All three diseases are types of transmissible  spongiform encephalopathies , so called because of the characteristic spongelike pattern of neuronal destruction that leaves  brain  tissue filled with holes.

7. Symptoms: Severe Mental Deterioration and dementia Involuntary muscle jerks or muscle movements Lack of coordination Problems with walking and balance Confusion Unusual Sensation Changes in vision Depression, Mood swings and anxiety Insomnia or changes in sleeping patterns

8. Transmission: Variant CJD. Organ or tissue transplants. Blood transfusion. Hormone transplant.

9. Exposure: Infected animal tissue. Contaminates medical equipment. Infected human tissue. Contaminated food.

10. Treatment and Diagnosis: There are few tests a doctor can use to help diagnose CJD: Electroencephalography(EEG) Physical Examination Brain biopsy or autopsy Cerebrospinal fluid based tests Magnetic resonance imaging (MRI) Symptoms relief Nursing care Pain management Supportive care Research and clinical trials

11. Preventions: Sterilization of medical equipment Screening of blood donors Safe handling of human tissue Proper disposal of infected material Avoiding consumption of contaminated animal products Implanting universal precautions Education and awareness Regulatory measures

12. Future directions(Prions): Development of effective treatment Understanding transmission Developing sensitive test for diagnosis Synthetic prions for research International collaboration

13. Thank you

14. Prions Presented by HAFSA RANI

15. Introduction to Prions Prions are misfolded proteins that can induce other normal proteins to misfold similarly. Unlike bacteria, viruses, and fungi, prions lack nucleic acids (DNA or RNA). Prions were first identified by Stanley B. Prusiner in the 1980s.

16. Structure of Prions Normal Prion Protein (  PrP C ): Normally found in the brain and other tissues; has a specific alpha-helical structure. Misfolded Prion Protein (  PrP Sc ): Abnormal form with a beta-sheet structure. Conversion Process: Misfolded  PrP Sc . can induce normal  PrP C  to convert into the abnormal form.

17. Mechanism of Prion Propagation Chain Reaction:   PrP^Sc interacts with PrP^C, converting it into more PrP^Sc. Aggregation:     Misfolded proteins accumulate in the brain, forming      plaques.  Neurodegeneration: Plaque buildup disrupts neuronal function, leading to brain damage .

18. Diseases Caused by Prions Human Diseases Animal Diseases Creutzfeldt-Jakob Disease (CJD) Variant CJD (vCJD) Gerstmann-Sträussler-Scheinker Syndrome (GSS) Fatal Familial Insomnia (FFI) Kuru Bovine Spongiform Encephalopathy (BSE) Scrapie in sheep Chronic Wasting Disease (CWD) in deer and elk

19. Transmission and Risk Factors Spontaneous Occurrence: Sporadic cases without known cause. Genetic Mutations: Inherited prion diseases due to genetic mutations in the PRNP gene. Contaminated Material: Transmission through consumption or exposure to infected tissues (e.g., contaminated surgical instruments, infected meat products).

20. Bovine Spongiform Encephalopathy (BSE) Common Name: Mad Cow Disease. First Identified: In the UK, mid-1980s. Affected Species: Primarily cattle, but can affect humans and other animals. Symptoms in Cattle: Changes in behaviour, coordination problems, difficulty walking, weight loss.

21. Transmission of BSE Primary Route: Through consumption of contaminated meat and bone meal (MBM) in cattle feed. Species Barrier: BSE can cross species barriers, notably affecting humans as variant Creutzfeldt-Jakob Disease (vCJD). Human Transmission: Humans can contract vCJD by consuming BSE-infected beef products.

22. Symptoms Memory loss Behavioural changes Coordination problems Dementia. Treatment Currently, no cure exists for prion diseases. Ongoing studies to understand prion biology and develop potential treatments.

23. Diagnosis and Prevention Diagnosis in Cattle:                                                        Post-mortem examination of brain tissue. Clinical Evaluation : Neurological exams and patient history. MRI and EEG : Brain imaging and electrical activity analysis. Biopsy : Post-mortem examination of brain tissue for definitive diagnosis. Prevention Measures: Ban on MBM in cattle feed. Surveillance and testing programs. Public awareness campaigns.

24. Impact of BSE Outbreak Economic Impact:  Severe economic losses in the cattle industry. Public Health:   Numerous cases of vCJD, causing public health crises. Regulatory Changes:   Stricter regulations on cattle feed and beef production.

25. The Future of Prion Research Understanding Mechanisms: Further research into the molecular mechanisms of prion propagation. Therapeutic Approaches: Developing drugs that can inhibit prion misfolding or promote their clearance. Diagnostic Advances: Creating better diagnostic tools for early detection of prion diseases.

26. THANK YOU...

27. Prions Submitted by: Kiran Submitted to: Dr. Aqsa Roll No. 1055 Department: MMG Semester: 4th

28. Prions A prion is a type of protein that can trigger normal proteins in the brain to fold abnormally. Prion diseases can affect both humans and animals and are sometimes spread to humans by infected meat products

29. The structure of PrPC is well studied, based on analyses of recombinant PrP, which is thought to mimic the structure of native PrPC. The mature protein contains an N-terminal, unfolded domain and a C-terminal, globular domain that consists of three α-helices and only a small, two-stranded β-sheet. • Structure of Prions

30. • This process –which can be underway for years before symptoms appear –likely causes the most common form of prion disease in people, sporadic Creutzfeldt-Jakob disease (CJD). Other forms of human prion diseases include variant CJD, fatal familial insomnia, Gerstmann-Straussler-Scheinker Syndrome and Kuru. Replication single PrPSc molecule binds to a single PrPC molecule and catalyzes its conversion into PrPSc. The two PrPSc molecules then come apart and can go on to convert more PrPC Types of Prions

31. Prions disease • Prion diseases occur when normal prion protein, found on the surface of many cells, becomes abnormal and clump in the brain, causing brain damage. This abnormal accumulation of protein in the brain can cause memory impairment, personality changes, and difficulties with movement.

32. What is the mechanism of kuru? • Kuru is a form of transmissible spongiform encephalopathy (TSE) caused by the transmission of abnormally folded proteins (prions), which leads to symptoms such as tremors and loss of coordination from neurodegeneration. A Fore child with advanced kuru.

33. The three discernible phases in kuruinclude • Ambulatory phase: Presents with features of cerebellar ataxia. ... • Sedentary phase: It starts when the patient is unable to stand without support and ends when unable to sit without support. ... • Terminal stage: The patient is bedridden and may develop dysphagia and incontinence.

34. How is kurutransmitted? • Kuru is caused by the accumulation of infectious, misfolded proteins called prions in the nervous system. The disease is spread through cannibalism of infected tissue (i.e. When an individual eats the human tissue of an infected individual)

35. Symptoms of kuruinclude • Arm and leg pain. • Coordination problems that become severe. • Difficulty walking. • Headache. • Swallowing difficulty. • Tremors and muscle jerks.

36. How is kuru diagnosed? • Diagnosis of kuru is primarily based on patient history and clinical presentation. Neurological exams can reveal ataxia, muscle jerks, as well as difficulty walking.

37. What is the treatment for kuru? • There were no treatments that could control or cure kuru, other than discouraging the practice of cannibalism. Currently, there are no cures or treatments for any of the other TSE diseases.

38. Development of kurudisease • It is also known as the “laughing sickness” due to the pathologic bursts of laughter which are a symptom of the disease. It is now widely accepted that kuru was transmitted among members of the Fore tribe of Papua New Guinea via funerary cannibalism

39. When was the last recorded case of kuru? • The end of cannibalism has put an end to kuru disease. The last case recorded was in 2005. [12] However, it remains the first described transmissible spongiform encephalopathy unraveling the mystery of other prion diseases.

40. How is kuru transmitted? • Brain tissue from individuals with kuru was highly infectious, and the disease was transmitted either through eating or by contact with open sores or wounds. Kuruis the Fore word for shiver.

41. What is the death rate of kuru? • The comparison of number of deaths from kuru in the period 1961–1963 and 1957–1959 showed a total 23% reduction, while, among the children, a 57% drop, while the kuru mortality rates decreased from 7.64 to 5.58 deaths per thousand.

42. University of Okara Assignment Virology Topic Prions Roll number 1048 Submitted by Hira Atif Submitted to Dr. Aqsa

43. Introduction Prions are infectious proteins that cause fatal neurodegenerative diseases in humans and animals. Their unique ability to self-propagate and induce misfolding of normal proteins leads to the formation of toxic aggregates.

44. Prions consist of an of a cellular protein called PrP. The misfolded PrP, known as PrPSc, is rich in and resistant to protease digestion. This conformational change is central to the pathogenicity of prions. Prion Structure

45. Transmission Routes Prions can be transmitted through various routes, including , , and . Moreover, they can be transmitted within and between species, leading to a wide range of prion diseases.

46. The pathogenesis of prion diseases involves the conversion of normal PrP into the . This triggers a cascade of events, including , , and ultimately, . Pathogenesis

47. Prion diseases manifest with a wide spectrum of clinical features, including , , and . The rapid progression and fatal outcome characterize these devastating neurodegenerative disorders. Clinical Manifestations

48. Poiron Disease Prion diseases are a group of rare, fatal brain disorders that affect humans and animals. Some of the prion diseases include: 1. Creutzfeldt-Jakob disease (CJD) 2. Variant Creutzfeldt-Jakob disease (vCJD) 3. Fatal Familial Insomnia (FFI) 4. Gerstmann-Sträussler-Scheinker syndrome (GSS)

49. FFI (Causes and Inheritance) Fatal Familial Insomnia (FFI) is a rare genetic prion disease that affects the brain, leading to gradual degeneration of the thalamus, a region crucial for sleep and wakefulness regulation. Here's a brief overview of FF I Causes and inheritance: - FFI is caused by a mutation in the PRNP gene, which codes for the prion protein. - It is inherited in an autosomal dominant pattern, meaning a single copy of the mutated gene is enough to cause the disease.

50. Symptoms - Gradual onset of insomnia (inability to sleep) and subsequent daytime sleepiness - Autonomic dysfunction (e.g., excessive sweating, high blood pressure) - Ataxia (coordination and balance problems) - Dysarthria (speech difficulties) - Weight loss - Eventual complete insomnia, leading to rapid deterioration and death

51. Diagnosis and Treatment - Diagnosis is based on genetic testing, medical history, and symptom evaluation. - There is no cure or effective treatment for FFI; management focuses on alleviating symptoms and supporting patients and their families.

52. management focuses on alleviating symptoms and supporting patients and their families. FFI is a devastating disease that progresses rapidly, typically leading to death within 12-18 months after symptom onset. Research continues to uncover the complexities of prion diseases, aiming to develop effective treatments and prevention strategies.

53. Diagnosis and Detection Diagnosing prion diseases can be challenging due to the lack of specific biomarkers and the insidious onset of symptoms. Current diagnostic approaches include neuroimaging, cerebrospinal fluid analysis, and post-mortem examination.

54. Developing effective therapeutics for prion diseases remains a formidable , . These strategies aim to challenge. Experimental approaches include , and mitigate the pathogenic effects of prions.

55. In conclusion, prion diseases represent a unique class of neurodegenerative disorders driven by the and of proteins. Understanding the and disease mechanisms is crucial for the development of effective diagnostic and therapeutic interventions. Conclusion