Most proteins fold into their native structure through defined pathways which
involve a limited number of transient intermediates. Intermediates play a relevant role in
the folding process; many diseases of genetic nature are in fact coupled with protein
misfolding, which favours formation of stable inactive intermediate species of a protein.
This review describes a number of diseases originated from protein misfolding and
briefly discusses the mechanism(s) responsible, at molecular level, for these
pathologies. It is also envisaged the native ⇄ molten globule transition since sometimes
the conversion of the native form into a compact intermediate state permits a protein to
carry out distinct physiological functions inside the cell. A non-native compact form of
cyt c, for example, is involved in the programmed cell death (apoptosis) after that the
protein is released from the mitochondrion; in addition, non-native forms of the protein
are involved in some of the disorders attributed to amyloid formation.
Keywords: Alzheimer’s disease, amyloid fibrils, apoptosis, conformational
diseases, cystic fibrosis, cytochrome c, energy landscapes, folding pathways,
intermediate states, Levinthal paradox, misfolding, molten globule,
neurodegenerative diseases, phospholipids, protein folding.