Prions

Howell D. Crisostomo, MD 1 July 2013 Medical Biochemistry San Beda College of Medicine

• To define prions and their role in disease causation • To differentiate the levels of protein structure and their biological/functional implications • To describe some techniques in protein structure analysis

• 47-year-old woman • 2-year history of progressive dementia, tiredness, lethargy and mild difficulty in falling asleep. • difficulty in communication and • unable to work • gradually progressive dementia and emotional lability. • increased appetite, and complex visual hallucinations. • A few weeks prior to consult, she become bedridden. • On neurological examination there was severe apathy, spontaneous myoclonus of the lower limbs, generalized hyperreflexia and bilateral Babinski signs.

• EEG displayed slow waves at 5 to 6 Hz, which were marked bilaterally in the frontal lobes and precentral regions • MRI of the brain showed bilateral atrophy of the cerebellar cortex, brainstem and cerebellum. On diffusion weighted imaging (DWI), there were high signals in the caudate nucleus, the putamen and the periventricular regions. • Biochemistry of the cerebrospinal fluid (CSF) was normal. • Western Blot analysis showed increased levels of PrPSC.

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Chronic salient symptoms with an abrupt progression Progressive dementia Myoclonic jerks Akinetic mutism Death

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PROTEINACEOUS INFECTIOUS PARTICLES infectious proteins transmissible spongiform encephalopathies Prion diseases are disorders of protein conformation, the most common of which in humans is called Creutzfeldt-Jakob disease (CJD)

1950s - Studies of progressive cerebellar ataxia in Fore people partaking in cannibalistic feast (Gajdusek and Zigas)

Similarities between Kuru and sheep scrapie at the neuropathologic and clnical levels. Slow viruses theory based on transmissibility of scrapie by Sigurdsson

1960’s an agent devoid of nucleic acid or protein. Griffith proposed mechanism for an “infectious...