Hereditary Spastic Paraplegia and Future Therapeutic Directions: Beneficial Effects of Small Compounds Acting on Cellular Stress.

摘要: Hereditary spastic paraplegia (HSP) is a group of inherited neurodegenerative conditions that share characteristic feature degeneration the longest axons within corticospinal tract, which leads to progressive spasticity and weakness lower limbs. Mutations over 70 genes produce defects in various biological pathways: axonal transport, lipid metabolism, endoplasmic reticulum (ER) shaping, mitochondrial function, endosomal trafficking. HSPs suffer from an adequate therapeutic plan. Currently treatments foreseen for patients affected by this pathology are physiotherapy, maintain outgoing tone, muscle relaxant therapies spasticity. Very few clinical studies have been conducted, it's urgent implement preclinical animal devoted pharmacological test screening, expand rose compounds potentially attractive trials. Small models, such as Drosophila melanogaster zebrafish, generated, analyzed, used model screening their effects. In work, we briefly described role HSP-linked proteins organization ER endomembrane system regulation homeostasis stress common pathological mechanism these HSP forms. We then focused our attention on pharmacodynamic pharmacokinetic features some recently identified molecules with antioxidant property, salubrinal, guanabenz, N-acetyl cysteine, methylene blue, rapamycin, naringenin, potential use future studies. Expanding models disease necessary give opportunity clinicians new molecules.