Protein therapy for Unverricht-Lundborg disease using cystatin B transduction by TAT-PTD. Is it that simple?
In this work we analysed the characteristics of the cell-permeable peptide TAT-PTD fused to cystatin B (CSTB) to evaluate its potential for protein therapy of Unverricht-Lundborg (UL) epilepsy. TAT-PTD-CSTB does not penetrate the cells despite initial evidence of time and concentration-dependent transduction. Therefore, it cannot be used as a form of replacement of the intracytoplasmic protein missing in UL. Importantly, we discuss precautions to avoid false-positive results when working with TAT-PTD for protein therapy of neurological diseases.
Andrade
Danielle M
DM
Department of Molecular and Medical Genetics, University of Toronto, Canada.
Scherer
Stephen W
SW
Minassian
Berge A
BA
D001812:Blood-Brain Barrier; D002462:Cell Membrane / Q000502:physiology; D055313:Cystatin B; D015891:Cystatins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D015853:Cysteine Proteinase Inhibitors; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D010957:Plasmids; D011485:Protein Binding; D021381:Protein Transport; D014161:Transduction, Genetic; D020194:Unverricht-Lundborg Syndrome / Q000628:therapy*
C524994:CSTB protein, human; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D015696:Gene Products, tat; D055313:Cystatin B