Investigación Sobre Orígen Genético De La Enfermedad Kuru Muerte Risueña

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Project progress
KURU, “Laughing death”
Introduction
The origin of this disease appears as a horror tale, it goes back to New Guinea on the year 1950, where strange funerary rituals were found among the Fore tribe. When a tribe member died, it was of great honor for the familiars to eat the brain of the defunct, in an act recognized ascannibalism.
This is how Kuru disease was perpetuated. Its name came from the Fore language, meaning “to shake from fear” Later on, the studies revealed that similar patterns of genetic transmission were found in Western populations. These, designated as fatal neurodegenerative prion protein (PrP) diseases include Gerstmann-Straussler syndrome and Cretzfeldt-Jacob disease, and have one commoninfectious agent: Prion
Prion diseases have been found in sheep, in human beings and in cows. The basic phenotype is an ataxia – a neurodegenerative disorder that is manifested by an inability to remain upright.
Objectives
1. Understand how a prion is structured and how it interacts with a biological system, by taking into account the existent databases and researches in the area.
2. Describethe prion structure and its relation with the genetic mutation that causes the disease.
3. Describe the molecular genetics of the acquisition of the disease, its polymorphisms and how can they confer resistance.
4. Describe the possible mechanism the PrPSc prion follows in order to affect the neuronal system of the brain.
General Background
The kuru symptoms can be described in 3distinct stages, as Gadjusek (1973) described are:
1. Ambulance stage: Includes unsteadiness of stance, gait, voice, hands, and eyes; deterioration of speech; quiver and shivering; in- coordination in lower extremities that moves slowly upward; and dysarthria (inability of speech).
2. Sedentary stage: In which the patient can no longer walk without support, there are more severe tremors andataxia (loss of coordination of the muscles), shock-like muscle jerks, outbursts of laughter, depression, and mental slowing.
3. Terminal stage: Patient is unable to sit up without support, the ataxia is much more severe, tremor, and dysarthria, urinary and faecal incontinence; difficulty swallowing and deep ulcerations appear.
As far as studied, all known prion diseases are fatal. Suchdiseases are often called spongiform encephalies since a common condition is that the brain becomes spongy and riddled with holes (Prusiner, 1995).
Nowadays, the prion disorders are attributed to PrPs, a mutated form of normal cellular prion protein (PrPC), caused by a single amino acid leucine which is substituted by the amino acid proline. The mutations are signaled at the 102nd codon ofchromosome 20 and have been linked to neurodegeneration, which is the main characteristic for all prion diseases.
It has been found as fundamental the study of prion structure and replication in order to understand these disorders and also to find possible therapies for these conditions.
Prion has been compared structurally with a virus (proteins surrounding a nucleic acid that encodes the proteins),but actually we already know that prion does not contain DNA or RNA. Further studies, by Cashman (1997), showed that PrPSc, compared with PrPC, does not dissolve in non-denaturing detergents and also it is partially resistant to proteases and survives in both acidic and basic media.
The reproduction mechanism is still unclear, but it is thought to function as a chain reaction: converted prionsconvert other proteins which they come into contact with on the interior of their respective cell membrane.
Furthermore, it has been observed that during the onset of the first case of kuru, around 1920s, women and children where predominantly affected, while men remain unaffected in much cases. Disease has been originated and spread from the cannibalistic rituals held by the Fore. Death...