Editorial: Hereditary Spastic Paraplegias: At the Crossroads of Molecular Pathways and Clinical Options

Many HSP proteins are structural or enzymatic components of endoplasmic reticulum (ER) membrane, suggesting that axonal ER dysfunction might be a key mechanism for HSP. [...]Oliva et al. and Napoli et al. characterize effects of HSP-related mutant genotypes on ER Ca2+ handling (Oliva et al.) and ER stress (Napoli et al.), and the latter study also shows pharmacological effects on the phenotypes. [...]this collection contains two review articles that draw on genetic and physiological work on model organisms. The work on the multimodal MRI is particularly intriguing. Besides confirming the ability of so-called “advanced MRI” to capture widespread structural alterations in the brains of HSP patients, it provides the problematic finding of a paradoxical increase in Fractional Anisotropy (reflecting in certain ways the degree of order and organization of the axons within the central nervous tissue) in the longitudinal assessment of these patients.