Cystatin B Involvement in Synapse Physiology of Rodent Brains and Human Cerebral Organoids

E. Penna, A. Cerciello, A. Chambery, R. Russo, FILIPPO MARIA CERNILOGAR, E. M. Pedone, C. Perrone-Capano, S. Cappello, Giaimo R. Di, M. Crispino

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

Cystatin B (CSTB) is a ubiquitous protein belonging to a superfamily of protease inhibitors. CSTB may play a critical role in brain physiology because its mutations cause progressive myoclonic epilepsy-1A (EPM1A), the most common form of progressive myoclonic epilepsy. However, the molecular mechanisms underlying the role of CSTB in the central nervous system (CNS) are largely unknown. To investigate the possible involvement of CSTB in the synaptic plasticity, we analyzed its expression in synaptosomes as a model system in studying the physiology of the synaptic regions of the CNS. We found that CSTB is not only present in the synaptosomes isolated from rat and mouse brain cortex, but also secreted into the medium in a depolarization-controlled manner. In addition, using biorthogonal noncanonical amino acid tagging (BONCAT) procedure, we demonstrated, for the first time, that CSTB is locally synthesized in the synaptosomes. The synaptic localization of CSTB was confirmed in a human 3D model of cortical development, namely cerebral organoids. Altogether, these results suggest that CSTB may play a role in the brain plasticity and open a new perspective in studying the involvement of CSTB deregulation in neurodegenerative and neuropsychiatric diseases.
Lingua originaleInglese
RivistaFrontiers in Molecular Neuroscience
Volume12
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • CSTB
  • EPM1A
  • cerebral organoids
  • local protein synthesis
  • synaptic plasticity
  • synaptosomes

Fingerprint

Entra nei temi di ricerca di 'Cystatin B Involvement in Synapse Physiology of Rodent Brains and Human Cerebral Organoids'. Insieme formano una fingerprint unica.

Cita questo