PRIONS-compressed

Overview

  • Title: Group 2 BS Biology 2C

Kuru Disease

  • Observation: In the 1950s, a medical officer in New Guinea identified a fatal disease in the Fore tribe called kuru (which means "trembling in fear").

  • Symptoms: Initial inability to walk, followed by loss of swallowing ability, significant weight loss, and death.

  • Cause: Kuru is a prion disease caused by abnormal prion proteins.

Understanding Prions

Definition and Properties

  • Prion: Short for Proteinaceous Infectious Particle, responsible for Transmissible Spongiform Encephalopathies (TSE), affecting the central nervous system.

  • Mechanism: Prions become abnormal, clump together, and cause brain damage, leading to memory issues, personality changes, and movement difficulties.

  • Fatal Nature: These disorders are often fatal; prion diseases are not well understood.

Structure of Prion Protein

  • Normal Form (PrPC): 200-250 amino acids, twisted into helices.

  • Infectious Form (PrPSc): Configured differently but composed of the same amino acids; significantly smaller than the smallest virus.

Genes Related to Prions

  • Prnp: Encodes normal prion protein (PrPC) on chromosome 2 (mice) and chromosome 20 (humans).

  • Prnd: Encodes Doppel, related to male reproductive health.

  • Sprn: Encodes a protein called Shadoo, expressed in the central nervous system.

Properties of Prions

  • Nucleic Acid: Prions do not contain DNA or RNA.

  • Resistance: Highly resistant to heat, chemicals, and biologically difficult to decompose. Remain in soil for years.

Discovery of Prions

  • Introduction: Discovered by Stanley Prusiner in 1982 during studies on scrapie (a sheep neurological disorder).

  • Nobel Prize: Prusiner was awarded the Nobel Prize in Physiology or Medicine in 1997 for this discovery.

  • Nature of Pathogenicity: Misfolded proteins cause similar proteins to misfold, leading to diseases.

Prion Forms

  • Two forms: PrP-sen (sensitive) and PrP-res (resistant)

  • PrP-sen: normal form found mainly in neurons.

  • PrP-res: Disease-causing form, resistant to breakdown, leading to spongiform disease.

Pathological Effects of Prions

  • Amyloid Fibers: Toxic to cells, leading to cell death. Abnormal protein accumulation results in neuron damage.

  • Cellular Response: Astrocytes digest neurons, leaving 'holes' in the brain, while amyloid fibers persist.

Prion Propagation

  • Mechanism: When a prion enters a healthy organism, it induces normal proteins to misfold, thereby creating more infectious prions, which then propagate.

  • Chain Reaction: This process triggers extensive production of prion forms, leading to widespread dysfunction.

Prion Diseases in Humans and Animals

Major Diseases

  • Transmissible Spongiform Encephalopathies (TSEs): Including Creutzfeldt-Jakob Disease (CJD) and Kuru. All are untreatable and fatal.

  • Bovine Spongiform Encephalopathy (BSE): Transmissible through contaminated feed leading to neurological degeneration in cattle, often resulting in severe symptoms and death.

Common Symptoms Across Prion Diseases

  • Memory issues, motor dysfunction, behavioral changes, and severe cognitive decline.

  • Infection typically leads to a rapid progression of symptoms, usually resulting in death within months.

Case Studies and Epidemiology

Case Report Highlights

  • CJD Case: Diagnosis based on clinical evaluation and CSF analysis, confirmed via autopsy.

  • Kuru: Symptoms evolve through stages, initiated by cannibalism in New Guinea.

  • Fatal Familial Insomnia (FFI): Linked to genetic mutations in the PRNP gene; symptoms include severe insomnia followed by cognitive decline.

  • BSE in Cattle: Transmitted through contaminated feed; major outbreaks recorded in Britain.

Prevention and Management

  • Prevention measures include regulations against importing cattle from BSE-affected regions, and stringent sterilization of medical instruments.

  • Current understanding of prion diseases focuses on managing symptoms, as no cures exist.

Conclusion

  • Prion diseases remain a significant area of medical research due to their unique properties, transmission mechanisms, and fatal outcomes.