Prions are proteinaceous infectious particles that lack nucleic acid and cause fatal neurodegenerative diseases. They exist in two forms - a normal cellular form (PrPc) and an abnormal disease-causing form (PrPsc). PrPsc has a different structure than PrPc which allows it to accumulate and convert PrPc into more PrPsc, ultimately causing neuropathology. Prion diseases affect both humans and animals and manifest as infectious, genetic, and sporadic disorders with varied clinical presentations. Common features include neurological deficits, dementia, and spongiform changes in the brain. Prions are extremely resistant to decomposition and differ from bacteria and viruses by being protein-only entities that propagate through conversion of

1. PRIONS
Dr. Shimna .C .S
Junior Resident
Department of Physiology

2. • Definition
• Structure
• Physiological functions of PrPc
• Chemical Properties
• Differences From Bacteria & Viruses
• Prion Diseases
– Neuropathology
– Features
• New Concepts

3. Definition
• Proteinaceous infectious particle
• Lacks nucleic acid
• Neurodegenerative diseases

4. • Discovered – STANLEY B PRUISNER (1982)
• Nobel Prize – 1997

5. Structure
• PrP-254 amino acids.
• PrPc : Normal cellular isoform
:Rich in alpha helix
• PrPsc : Disease causing isoform
:Rich in beta pleated
• Both PrPC and PrPSc -209 AA

6. PrPc PrPsc
• Cellular
• Dominant alpha helix
• Easily soluble
• Monomeric
• Digested by Proteases
• Gene PRNP (short arm
of chromosome 20)
• Disease causing
• Beta pleated
• Insoluble
• Multimeric
• Resistant to digestion
• Reproduce by binding
to PrPC and stimulating
conversion of PrPC into
PrPsc

9. Physiological functions of PrPc
• Modulate
– 1) Functions of the nervous and immune systems,
including memory and inflammatory reactions
– 2) Cell proliferation, differentiation, and sensitivity to
programmed cell death both in the nervous and immune
systems, as well as in various cell lines
– 3) Activity of numerous signal transduction pathways,
including cAMP/protein kinase A
– 4) Antioxidative ( ncbi )

10. • Antioxidative
PrPC + Cu (Copper)

Resistance to oxidative stress

Prevent neuronal dysfunction

11. Chemical Properties
• Limited proteolysis of PrPSc - PrP27-30(142 AA)
-Protease Resistant.
• Presence of detergent PrP27-30 Amyloid
• Prion Rods – limited proteolysis & detergent extraction of
PrPSc

12. Amyloid & Prion rods
• Similar ultrastructural morphology
• Green gold birefringence with Congo red dye

13. Differences From Bacteria & Viruses
• PrP isoforms are encoded by a chromosomal
gene.
• Do not contain nucleic acid.
• Extremely resistant to heat and chemicals.
• Difficult to decompose biologically;survive in
soil for many years.

14. Prion Diseases
Human
• Kuru
• Creutzfeldt-Jakob disease
– Sporadic
– Iatrogenic
– Variant
– Familial
• Gerstmann-Straussler-
Scheinker disease
• Fatal familial insomnia
• Sporadic fatal insomnia
Animals
• Scrapie
• Bovine spongiform
encephalopathy
• Transmissible mink
encephalopathy
• Chronic wasting disease
• Feline spongiform
encephalopathy
• Exotic ungulate
encephalopathy

15. • SPORADIC - 85%
– CJD
• FAMILIAL – 15%
– GSS, FFI
• TRANSMISSIBLE - rare
– KURU ,BSE

16. Neuropathology
• Gross – no detectable abnormality
• Microscopy –
– Spongiform degeneration
– Astrocytic gliosis
– Amyloid plaques
– Florid plaques : vCJD

17. Clinical Features
• Deficits in higher cortical function
• Dementia
• Visual impairment
• Cerebellar gait and coordination deficits
• Extrapyramidal dysfunction
• Myoclonus

18. New concepts
• Only known infectious pathogens devoid of nucleic acid
• Manifest as infectious, genetic, and sporadic disorders; no
other group of illnesses with a single etiology presents with
such a wide spectrum of clinical manifestations.
• Prion diseases result from the accumulation of PrPSc, the
conformation of which differs substantially from that of its
precursor, PrPC

19. References
• Harrison's
PRINCIPLES OF INTERNAL MEDICINE
• Harper’s TEXTBOOK OF BIOCHEMISTRY

20. THANK YOU