European Journal of Biological Sciences 6 (3): 59-65, 2014 ISSN 2079-2085 © IDOSI Publications, 2014 DOI: 10.5829/idosi.ejbs.2014.6.03.85206 Corresponding Author: Vikash Kumar, Central Inland Fisheries Research Institute (CIFRI), Barrackpore-700120 India. 59 Infectious Protein Particle Prions Vikash Kumar and Suvra Roy Central Inland Fisheries Research Institute (CIFRI), Barrackpore-700120 India Abstract: Transmissible spongiform encephalopathies (TSEs), otherwise known as prion disorders, are fatal diseases causing neurodegeneration in a wide range of mammalian hosts, including humans. The causative agent prions are thought to be composed of a rogue isoform of the endogenous prion protein (PrP). Prion diseases or TSEs are a group of rare but fatal neurological disorders that affect humans and animals. Whether sporadic, inherited or acquired, these illnesses generally correlate with the accumulation of misfolded PrP in the brain and the appearance of widespread neurodegeneration after long incubation times. The classical histopathological landmarks of TSEs are spongiform vacuolation, neuronal loss and astrocytic gliosis, whereas the main clinical manifestations in humans include progressive dementia, cerebellar ataxia and myoclonus. Interestingly, although such symptoms are also observed in more common neurodegenerative disorders like Alzheimer's disease (AD) and Parkinson's disease (PD); prion diseases have received special attention because of their infectious nature and the associated risk of epidemics. Key words: Prion Diseases Misfolded Neurodegeneration Spongiform Vacuolation INTERODUCTION and instead accumulate within nerve cells till destroying Prion, an abnormal form of a normally harmless causes brain tissue to become filled with holes in a protein found in the brain that is responsible for a variety sponge like, or spongiform, pattern. of fatal neurodegenerative diseases of both animals In 1982, Prion protein isoform PrP was and humans called transmissible spongiform identified as the major constituent of infective encephalopathies. In the early 1980s the American fractions purified from hamster brain homogenates neurologist Stanley B. Prusiner and colleagues identified [1]. Subsequent characterization revealed that the the “proteinaceous infectious particle,” a name that was pathogenic protein was host-encoded and not the shortened to “prion” (Pronounced “pree-on”). Prions can product of a viral gene, as it had been assumed enter the brain through infection, or they can arise from previously [2, 3]. It was also established that PrPSc is mutations in the gene that encodes the protein. post-translationally derived from PrP [4]. Thus, Once present in the brain prions multiply by inducing although the two isoforms differ greatly in their spatial benign proteins to refold into the abnormal shape. conformation [5], they have the same amino acid This mechanism is not fully understood, but another sequence and are encoded by the same single-copy gene, protein normally found in the body may also be involved. Prnp [6]. Under normal conditions, PrP is a glycoprotein The normal protein structure is thought to consist of a tethered to the outer plasma membrane by a number of flexible coils called alpha helices. In the prion glycosylphosphatidylinositol (GPI) anchor. Its unique protein some of these helices are stretched into flat molecular structure, studied by nuclear magnetic structures called beta strands. The normal protein resonance (NMR) and crystallographic techniques, can be conformation can be degraded rather easily by cellular roughly divided into two halves: a flexible N-terminal enzymes called proteases, but the prion protein shape is domain rich in repetitive motifs and a C-terminal globular more resistant to this enzymatic activity. Thus, as prion domain containing a characteristic array of three -helices proteins multiply they are not broken down by proteases and two -sheets. At the centre of the polypeptide chain, them. Progressive nerve cell destruction eventually Sc C C