PRNP and amyotrophic lateral sclerosis: The disease-causing misfolded proteins are generated over the course of aging by post-translational modifications (for example, endoproteolytic cleaves and phosphorylation) of native proteins (for example, amyloid β and tau in AD) or genetic mutations of otherwise non-pathogenic proteins (for example, HTT in HD, α-synuclein in PD, PrPC in prion disease and SOD1 and TDP-43 in ALS).