Neural Regeneration Research ›› 2019, Vol. 14 ›› Issue (1): 62-64.doi: 10.4103/1673-5374.243708

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Neuroprotective modulation of the unfolded protein response in Marinesco-Sjögren syndrome: PERK signaling inhibition and beyond

Elena Restelli1, Antonio Masone1, Michele Sallese2, Roberto Chiesa1   

  1. 1 Department of Neuroscience, IRCCS – Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy;
    2 Department of Medical, Oral and Biotechnological Sciences, Università “G. d’Annunzio”, Chieti, Italy; CeSI-MeT, Center for Research on Ageing and Translational Medicine, Università “G. d’Annunzio”, Chieti, Italy
  • Online:2019-01-15 Published:2019-01-15
  • Contact: Elena Restelli, PhD, elena.restelli@marionegri.it; Roberto Chiesa, PhD, roberto.chiesa@marionegri.it.
  • Supported by:

    This work was supported by a grant from Fondazione Telethon, No. GGP12220 (to MS and RC).

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Abstract:

Individuals with Marinesco-Sjögren syndrome (MSS; OMIM 248800), a genetic disease of infancy, suffer var-ious disabilities, including loss of motor coordination due to cerebellar degeneration, and skeletal muscle weak-ness. After a progressive phase, symptoms stabilize and patients live to old age. Therefore, any pharmacological treatment that delays or attenuates cerebellar degenera-tion and/or muscle pathology can significantly improve their quality of life. We recently found that inhibiting the protein kinase RNA-like endoplasmic reticulum kinase (PERK) delays cerebellar degeneration, and ameliorates motor function and muscle pathology in a MSS mouse model. This is the first preclinical study of a pharmacological treatment for MSS. Here we summarize our findings, and discuss how this therapeutic strategy might be improved for effective treatment.