Disease prion diseases

Alzheimer s disease, Parkinson disease, prion diseases (Creutzfeld-Jacob in humans, scrapie in sheep), Huntington disease, dementia with Levy s bodies, sclerosis multiplex and amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and vascular dementia are the most commonly occurring neurodegenerative diseases, with different (and often unknown) pathophysiology, creating serious health care problems and... 

Keywords Alzheimer s disease Amyotrophic lateral sclerosis Creutzfeldt-Jakob disease Huntington s disease Multiple sclerosis Parkinson s disease Prion diseases Striatoni-gral degeneration Synucleinopathies Tauopathies... 

Like other neurodegenerative disorders, such as Alzheimer s and Parkinson s disease, prion diseases are characterized by the formation and accumulation of an aberrantly folded protein in the brain. However, a unique feature of prion diseases is their transmissibility. Prions (acronym for proteinaceous infectious particles) are mainly composed of PrPSc, polysaccharides, and lipids, but lack nucleic acids longer than 25 nucleotides, arguing against an essential role for DNA/RNA in mediating infectivity [35, 36]. Indeed, recent experiments support the protein-only hypothesis recombinant PrP expressed in and purified from bacteria and subsequently misfolded in vitro can transmit the disease [37-40]. 

If the protein fails to fold properly, its shape is incorrect and it cannot perform its intended function. Aberrations in protein folding appear to contribute to human diseases. Among these are Alzheimer s disease, prion diseases, emphysema and cirrhosis, amyelotrophic lateral sclerosis (Lou Gehrig s disease), cystic fibrosis, some tumors, and osteogenesis imperfecta (King et al., 2002). The prion that seems to cause ovine transmissible spongiform encephalopathy, for instance, appears as a pleated sheet rather than a smooth helix. 

Comment. Other possibilities for his presenting symptoms inclnde small strokes (including mnlti-infarct dementia), chronic subdural hematoma, low-grade tumor metastases, B12 deficiency, atypical Alzheimer disease, prion disease, and chronic fungal or other infection. 

History or ciinicai evidence of prion disease Prion disease risk factors... 

Biological/Medical Applications Detecting nucleic acids diagnosis and selective tissue necrosis treating cancer, mahbnned proteins causing neurodegenerative disease, prion disease ... 

The transmissible spongiform encephalopathies, or prion diseases, are fatal neurodegenerative diseases characterized by spongiform changes, astrocytic gliomas, and neuronal loss resulting from the deposition of insoluble protein aggregates in neural cells. They include Creutzfeldt-Jakob disease in humans, scrapie in... 

Prions—protein particles that lack nucleic acid— cause fatal transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, scrapie, and bovine spongiform encephalopathy. Prion diseases involve an altered secondary-tertiary strucmre of a namrally occurring protein, PrPc. When PrPc interacts with its pathologic isoform PrPSc, its conformation is transformed from a predominantly a-helical strucmre to the P-sheet strucmre characteristic of PrPSc. 

Burkhard P, Stetefeld J, Strelkov SV Coiled coils A highly versatile protein folding motif. Trends Cell Biol 2001 11 82. Collinge J Prion diseases of humans and animals Their causes and molecular basis. Annu RevNeurosci 2001 24 519. 

Soto C Alzheimer s and prion disease as disorders of protein conformation Implications for the design of novel therapeutic... 

Prusiner S.B. (1996) Molecular biology and pathogenesis of prion disease. Trends Biochem Sci, 21, 482-487. 

Prion diseases resulting in encephalopathy can be transmitted between individuals within species (more rarely between species) [26-28], A conformational variant of the normal cellular protein PrPs (PrPc) (protease-sensitive or cellular) is believed to catalyze [29] or nucleate [30-33] conversion to the pathological form, PrPR (protease-resistant). This highly unusual nongenetic mode of transmission of an infectious agent has been strongly debated [29]. The observation of multiple examples of nucleated catalysis of aberrant polymerization of protein subunits has... 

Human prion disease models have also been developed in mice [154,155]. Crossing the species barrier into an experimentally accessible animal system, the prions responsible for Creutzfeldt Jakob disease, new variant CJD, Gerstmann-Straussler-Scheinker disease, and fatal familial insomnia produce a reproducible time-dependent neuronal degeneration leading to death. 

Kellershohn N, Laurent M. Species barrier in prion diseases a kinetic interpretation based on the conformational adaptation of the prion protein. Biochem J 1998 334 539-545. 

Come JH, Fraser PE, Lansbury PT, Jr. A kinetic model for amyloid formation in the prion diseases importance of seeding. Proc Natl Acad Sci USA 1993 90 5959-5963. 

DeArmond SJ, Ironside JW. Neuropathology of prion diseases. In Prusiner SB, ed. Prion Biology and Diseases. Vol. 38. Cold Spring Harbor, NY Cold Spring Harbor Press, 1999 585-652. 

Keohane C. The human prion diseases. A review with special emphasis on new variant CJD and comments on surveillance. Clin Exp Pathol 1999 47 125-132. 

Raeber AJ, Brandner S, Klein MA, Benninger Y, Musahl C, Frigg R, Roeckl C, Fischer MB, Weissmann C, Aguzzi A. Transgenic and knockout mice in research on prion diseases. Brain Pathol 1998 8 715-733. 

Suggested Alternatives for Differential Diagnosis Bartonellosis, brucellosis, other causes of encephalitis, coxsackieviruses, cryptococcosis, cysticercosis, cytomegalovirus, histoplasmosis, legionellosis, leptospirosis, listeria, lyme disease, malaria, rabies, tuberculosis, mumps, stroke, metabolic encephalopathy, Reye syndrome, Bartonella infection, Naegleria infection, Ebstein-Barr virus, prion disease, toxic ingestions, and AIDS. 

NEURODEGENERATIVE a-SYNUCLEINOPATHIES AND TAUOPATHIES 745 NEUROTRANSMITTERS AND DISORDERS OF THE BASAL GANGLIA 761 NEUROBIOLOGY OF ALZHEIMER S DISEASE 781 MOLECULAR BASIS OF PRION DISEASES 791... 

CREUTZFELDT-JAKOB DISEASE AND OTHER PRION DISEASES 662... 

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