Prion diseases cell death

The precise structure of the infectious agent and the cause of neuronal cell death in prion disease remain unclear. The current working hypothesis is that an abnormal... 

Townsend L, Ongjni E, Wenk G (2004) Novel therapeutic opportunities for Alzheimer s disease focus on nonsteroidal anti-inflammatory drugs. FASEB J 19 1592-1601 Trejo JL, Cairo E, Nunez A, Torres-Aleman 1 (2002) Sedentary hfe impairs self-reparative processes in the brain the role of serum insulin-like growth factor-1. Rev Neurosci 13 365-374 Tsuboi Y, Doh-ura K, Yamada T (2009) Continuous intraventricular infusion of pentosan polysulfate clinical trial against prion diseases. Neuropathology 29(5) 632-636 Tsujimoto Y, Shimizu S (2003) Role of the mitochondrial membrane permeability transition in cell death. Apoptosis 12 835-840... 

Chapter 7 begins with the assertion that biology thrives near a movable cusp of insolubility and that excursions too far either direction into the realm of insolubility or of solubility spells disease and death. For example, sickle cell disease represents an excursion too far into the realm of insolubility, as do the more ominous prion diseases of Alzheimer s disease, and mad cow disease. Blood clotting is a special example of thriving at the cusp of insolubility. This chapter also discusses molecular chaperones... 

Another class of diseases is due to stmctural changes of proteins mediated by other molecules, so-called prions. As there is a strong causal coimection between the three-dimensional stracture of a protein and its biological function, refolding can cause the loss of functionality, A possible consequence is the death of cells. Examples for prion diseases in the brain are bovine spongiform encephalopathy (BSE) and its human form Creutzfeldt-Jakob disease (CID)." ... 

Alzheimer s, Parkinson s and prion diseases are characterized by neuronal loss and protein aggregates that may or may not be fibrillar. However, the exact identity of the neurotoxic species and the mechanism by which it kills neurons are unknown. Biophysical studies support the emerging notion that a prefibrillar oligomer (protofibril) may be responsible for cell death and that the fibrillar form that is typically observed post mortem may actually be neuroprotective. The laboratory of Peter Lansbury suggests that a subpopulation of the soluble protofibrils may function as pathogenic pores that might have the ability to permeabilize cell or mitochondrial membranes 35). Annular, pore-like structures are observed in familial mutants of a-synuclein (Parkinson s disease) and Alzheimer s precursor protein (Alzheimer s disease) as shown in Plate 3A 56). 

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