TY - JOUR
T1 - A new interpretative paradigm for conformational Protein Diseases
AU - Agnati, Luigi Francesco
AU - Guidolin, Diego
AU - Woods, Amina S.
AU - Ciruela, Francisco
AU - Carone, Chiara
AU - Vallelunga, Annamaria
AU - Escuela, Dasiel Oscar Borroto
AU - Genedani, Susanna
AU - Fuxe, Kjell
PY - 2013
Y1 - 2013
N2 - Conformational Protein Diseases (CPDs) comprise over forty clinically and pathologically diverse disorders in which specific altered proteins accumulate in cells or tissues of the body. The most studied are Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, prion diseases, inclusion body myopathy, and the systemic amyloidoses. They are characterised by three dimensional conformational alterations, which are often rich in β structure. Proteins in this non-native conformation are highly stable, resistant to degradation, and have an enhanced tendency to aggregate with like protein molecules. The misfolded proteins can impart their anomalous properties to soluble, monomeric proteins with the same amino acid sequence by a process that has been likened to seeded crystallization. However, these potentially pathogenic proteins also have important physiological actions, which have not completely characterized. This opens up the question of what process transforms physiological actions into pathological actions and most intriguing, is why potentially dangerous proteins have been maintained during evolution and are present from yeasts to humans. In the present paper, we introduce the concept of mis-exaptation and of mis-tinkering since they may help in clarifying some of the double edged sword aspects of these proteins. Against this background an original interpretative paradigm for CPDs will be given in the frame of the previously proposed Red Queen Theory of Aging.
AB - Conformational Protein Diseases (CPDs) comprise over forty clinically and pathologically diverse disorders in which specific altered proteins accumulate in cells or tissues of the body. The most studied are Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, prion diseases, inclusion body myopathy, and the systemic amyloidoses. They are characterised by three dimensional conformational alterations, which are often rich in β structure. Proteins in this non-native conformation are highly stable, resistant to degradation, and have an enhanced tendency to aggregate with like protein molecules. The misfolded proteins can impart their anomalous properties to soluble, monomeric proteins with the same amino acid sequence by a process that has been likened to seeded crystallization. However, these potentially pathogenic proteins also have important physiological actions, which have not completely characterized. This opens up the question of what process transforms physiological actions into pathological actions and most intriguing, is why potentially dangerous proteins have been maintained during evolution and are present from yeasts to humans. In the present paper, we introduce the concept of mis-exaptation and of mis-tinkering since they may help in clarifying some of the double edged sword aspects of these proteins. Against this background an original interpretative paradigm for CPDs will be given in the frame of the previously proposed Red Queen Theory of Aging.
KW - Aging
KW - Exaptation
KW - Neurodegenerative diseases
KW - Prions
KW - Protein aggregation
KW - Protein conformation
KW - Tinkering
UR - http://www.scopus.com/inward/record.url?scp=84878545999&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878545999&partnerID=8YFLogxK
U2 - 10.2174/1389203711314020006
DO - 10.2174/1389203711314020006
M3 - Article
C2 - 23441893
AN - SCOPUS:84878545999
SN - 1389-2037
VL - 14
SP - 141
EP - 160
JO - Current Protein and Peptide Science
JF - Current Protein and Peptide Science
IS - 2
ER -