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1. (WO2018160662) A NOVEL NERVOUS SYSTEM-SPECIFIC TRANSMEMBRANE PROTEASOME COMPLEX THAT MODULATES NEURONAL SIGNALING THROUGH EXTRACELLULAR SIGNALING VIA BRAIN ACTIVITY PEPTIDES

Pub. No.:    WO/2018/160662    International Application No.:    PCT/US2018/020173
Publication Date: Sat Sep 08 01:59:59 CEST 2018 International Filing Date: Thu Mar 01 00:59:59 CET 2018
IPC: A61K 51/00
A61K 38/02
A61K 31/69
A61P 25/00
Applicants: THE JOHNS HOPKINS UNIVERSITY
Inventors: MARGOLIS, Seth
RAMACHANDRAN, Kapil V.
Title: A NOVEL NERVOUS SYSTEM-SPECIFIC TRANSMEMBRANE PROTEASOME COMPLEX THAT MODULATES NEURONAL SIGNALING THROUGH EXTRACELLULAR SIGNALING VIA BRAIN ACTIVITY PEPTIDES
Abstract:
The inventors surprisingly found that neural stimulation caused the synthesis and degradation of proteins into peptides which were then secreted into the cell media within minutes of stimulation by a novel neural membrane bound proteasome (NMP). These secreted, activity-induced, proteasomal peptides (SNAPPs) range in size from about 500 Daltons to about 3000 Daltons. Surprisingly none of the peptides appear to be those previously known to have any neuronal function. Moreover, these SNAPPs have stimulatory activity and are heretofore a new class of signaling molecules. The present invention provides methods of modulating NMP function, including in cases of NMP associated disease or disorder of neuronal cells, by stimulating or inhibiting NMP function. The present invention also provides methods for stimulation or enhancing cognitive function using SNAPPs, and methods for treating of NMP related diseases using SNAPPs.