Wrinkles and folds of the prion protein

In this issue of Neurology , Walz et al.1 report that a variant form (i.e., allele) of the prion protein gene ( PRNP ) that encodes serine (S) instead of asparagine (N) at codon 171 is associated with the development of mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) and the response to surgical treatment. Although varied insults such as prolonged febrile seizures, abnormal brain development, and perinatal hypoxia have been implicated in MTLE-HS, the underlying cause for this disorder remains unknown. The presence of the N171S polymorphism of PRNP is presumed to increase the predisposition of an individual to insults that lead to MTLE-HS, suggesting that the prion protein has a functional role in the maintenance of a normal neurophysiologic state. The best known feature of the normal cellular form of the prion protein, PrPC, is its potential to misfold to a protease-resistant conformation (PrP …

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