Misfolding and aggregation of
prion proteins is linked to a number of
neurodegenerative disorders such as
Creutzfeldt-Jacob disease (CJD) and its variants:
Kuru,
Gerstmann-Straussler-Scheinker syndrome and
fatal familial insomnia. In
prion diseases, infectious particles are
proteins that propagate by transmitting a misfolded state of a
protein, leading to the formation of aggregates and ultimately to neurodegeneration.
Prion phenomenon is not restricted to humans. There are a number of
prion-related diseases in a variety of mammals, including
bovine spongiform encephalopathy (BSE, also known as "
mad cow disease") in cattle. All known
prion diseases, collectively called
transmissible spongiform encephalopathies (TSEs), are untreatable and fatal.
Prion proteins were also found in some fungi where they are responsible for heritable traits.
Prion proteins in fungi are easily accessible and provide a powerful model for understanding the general principles of
prion phenomenon and molecular mechanisms of mammalian
prion diseases. Presently, several fundamental questions related to
prions remain unanswered. For example, it is not clear how
prions cause the disease. Other unknowns include the nature and structure of infectious agent and how
prions replicate. Generally, the phenomenon of misfolding of the
prion protein into infectious conformations that have the ability to propagate their properties via aggregation is of significant interest. Despite the crucial importance of misfolding and aggregation, very little is currently known about the molecular mechanisms of these processes. While there is an apparent critical need to study molecular mechanisms underlying misfolding and aggregation, the detailed characterization of these single molecule processes is hindered by the limitation of conventional methods. Although some issues remain unresolved, much progress has been recently made primarily due to the application of nanoimaging tools. The use of nanoimaging methods shows great promise for understanding the molecular mechanisms of
prion phenomenon, possibly leading toward early diagnosis and effective treatment of these devastating diseases. This review article summarizes recent reports which advanced our understanding of the
prion phenomenon through the use of nanoimaging methods.