Membrane-Related Diseases - Membrane Biophysics, Biological and Medical Physics, Biomedical Engineering - page 155

Fig. 7.2 Ribbon diagram of the structure of SHaPrP(90-231) based on the NMR structure in aqueous
solution [ 19 ]. The two tryptophan residues (Trp99 and Trp145) are highlighted in ball-and-stick
representation. The structure shows the three main helices ( A , B ,and C ), and the two antiparallel
β -strands ( S1 and S2 ). This figure has been adapted from the Ref. [ 38 ] with permission from the

publisher

on a sponge-like texture. This is due to a type of infectious protein called a prion.
The normal tissue structure is disrupted due to the formation of plaques (amyloid) by
extracullular aggregation of prions within the central nervous system. Prions are mis-
folded proteins which replicate by converting their properly folded counterparts into
the disease-associated, prion form [ 36 ]. Astrogliosis, inflammatory reaction loss, etc.
are among the most important changes at the cellular level [ 6 ]. The healthy organism
becomes affected through the penetration of prions into the healthy organisms. The
newly misfolded prion forms induce further misfoldings and sometimes may trigger
chain reactions which at the end may produce large amounts of misfolded or prion
form states [ 4 ]. Although the incubation times of prion-related diseases are quite long
due to the chain transmission of prion states, once the symptoms appear it is often too
late to stop it as the diseases reaches an out-of-control status. At this stage, the rapid
progression of disease may easily cause uncontrollable levels of damage in various
parts of the brain. Death becomes inevitable due to the various unrepairable disor-
dered protein states [ 3 ]. All prion diseases are considered to be fatal and untreatable
using existing medical procedures.
Prions enter into the tissue structure, which is why their effects on lipids are very
important. Various research groups are actively working to better understand the
membrane effects of lipids. For example, the binding of the Syrian hamster prion
protein SHaPrP(90-231) (see the structure in Fig. 7.2 ) to model lipid membranes
was investigated by tryptophan fluorescence by Sanghera and Pinheiro [ 38 ], and
this study provides important insights into prion-lipid interactions. This study sug-
gests that an interaction of prion protein (PrP) with lipid membranes could play
a role in PrP conversion. These investigators considered all of zwitterionic lipid
membranes, raft-like membranes, cholesterol, etc and reported that the binding of