Amyloidogenic metal-binding proteins: new investigative pathways.
Neurodegenerative diseases remain perplexing and problematic for modern research. Those associated with amyloidogenic proteins have often been lumped together simply because those proteins aggregate. However, research has identified a more logical reason to group some of these diseases together. The associated proteins not only aggregate, but also bind copper. The APP (amyloid precursor protein) binds copper in an N-terminal region. Binding of copper has been suggested to influence generation of beta-amyloid from the protein. PrP (prion protein) binds copper, and this appears to be necessary for its normal function and might also reduce its probability of conversion into an infectious prion. alpha-Synuclein, a protein associated with Parkinson's disease, also binds copper, but, in this case, it potentially increases the rate at which the protein aggregates. The similarities between these proteins, in terms of metal binding, has allowed us to investigate them using similar approaches. In the present review, we discuss some of these approaches.
Davies
Paul
P
Department of Biology and Biochemistry, University of Bath, Bath, UK.
Fontaine
Sarah N
SN
Moualla
Dima
D
Wang
Xiaoyan
X
Wright
Josephine A
JA
Brown
David R
DR
D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D003141:Communicable Diseases / Q000378:metabolism; D004563:Electrochemistry; D006801:Humans; D008670:Metals / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D000682:Amyloid; D008670:Metals; D011506:Proteins