Protein misfolding is the hallmark of a large number of neurodegenerative
diseases and is characterized by the presence of amyloid inclusions composed of
aggregates of misfolded proteins in specific areas of the brain. The formation of those
aggregates involves a multistep process that is exacerbated during periods of cellular
stress. Cells have several mechanisms to regulate protein quality control that also serve
as a defense line to prevent the accumulation of misfolded proteins; failures in these
defenses are frequently involved in neurodegeneration. Another intriguing feature of
neurodegenerative diseases, which have misfolded proteins as etiological agents, is the
presence of similarities with prion diseases. Prions are unconventional infectious agents
composed entirely from a misfolded form of a native protein that has the capacity to
provoke and propagate to neighboring cells or even to other organisms. Nowadays, a
large body of evidence has shown that most of the misfolded proteins found in
degenerated brains behave as prion-like proteins, promoting misfolding and
consequently, the aggregation of native protein forms which can spread to other cells or
brain regions. However, unlike prion diseases, the prion-like properties of misfolded
proteins are unable to naturally infect other organisms. Taken together,
neurodegenerative diseases share many characteristics, of which protein misfolding is
the most important. This feature has huge therapeutic implications since it raises the
possibility to treat different diseases with drugs targeted to impair, block or revert
protein misfolding.
Keywords: Protein aggregates, oligomers, fibrils, amyloid plaques, tangles, Lewy
bodies, chaperones, protein degradation, oxidative damage.
