Protein misfolding
neurodegenerative diseases arise through neurotoxicity induced by aggregation of host
proteins. These conditions include
Alzheimer's disease,
Huntington's disease,
Parkinson's disease,
motor neuron disease,
tauopathies and
prion diseases. Collectively, these conditions are a challenge to society because of the increasing aged population and through the real threat to human food security by animal
prion diseases. It is therefore important to understand the cellular and molecular mechanisms that underlie
protein misfolding-induced neurotoxicity as this will form the basis for designing strategies to alleviate their burden.
Prion diseases are an important paradigm for neurodegenerative conditions in general since several of these maladies have now been shown to display
prion-like phenomena. Increasingly, cell cycle activity and the DNA damage response are recognised as cellular events that participate in the neurotoxic process of various
neurodegenerative diseases, and their associated animal models, which suggests they are truly involved in the pathogenic process and are not merely epiphenomena. Here we review the role of cell cycle activity and the DNA damage response in neurodegeneration associated with
protein misfolding diseases, and suggest that these events contribute towards
prion-induced neurotoxicity. In doing so, we highlight PrP transgenic Drosophila as a tractable model for the genetic analysis of transmissible mammalian
prion disease.