Peptide inhibitors and methods for inhibiting protein aggregation in neurons and neurodegenerative diseases
AssigneesThe Governing Council of the University of Toronto, University Health Network
InventorsPhilip Kim, Satra Nim, Carlos Corbi Verge, Suneil K. Kalia, Lorraine V. Kalia
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Abstract
Provided herein is a method of decreasing a-syn levels and/or decreasing a-syn toxicity in a cell, the method comprising contacting the cell with a charged multivesicular body protein 2B: a-synuclein (CHMP2B:a-syn) inhibitor and a method of inhibiting neural degeneration, the method comprising administering to a subject in need thereof a charged multivesicular body protein 2B: a-synuclein (CHMP2B:a-syn) inhibitor.
Claims62
A method of decreasing a-syn levels and/or decreasing a-syn toxicity in a cell, the method comprising contacting the cell with a charged multivesicular body protein 2B:
- a-synuclein (CHMP2B:a-syn) inhibitor.
A method of inhibiting neural degeneration, the method comprising administering to a subject in need thereof a charged multivesicular body protein 2B:
- a-synuclein (CHMP2B:a-syn) inhibitor.
The method of any preceding claim wherein the peptide of a) consists of a sequence of 5 to 25, 5 to 20, 4 to 15, 4 to 10, 7 to 20, 7 to 15 or 7 to 10 amino acids or the peptide of b) consists of a sequence 5 to 60, 5 to 50, 5 to 40, 5 to 30, 5 to 25, 5 to 20, 5 to 15, 5 to 10, 7 to 30, 7 to 25, 7 to 20, or 7 to 15 amino acids.
A peptide or a polypeptide comprising or consisting of a) a MIT-Interacting Motif (MIM) sequence or a sequence with at least 50% sequence identity to said MIM sequence or b) an a-syn interaction sequence or a sequence with at least 50% sequence identity to said a-syn interaction sequence, wherein the peptide inhibits CHMP2B-CHMP2B interaction or CHMP2B-a-syn interaction by at least 50%, wherein the peptide optionally comprises one or more exogenous residues, optionally interspersed for example for one or more, optionally two, cysteines.
A charged multivesicular body protein 2B:
- a-synuclein (CHMP2B:a-syn) inhibitor comprising a peptide comprising a) a MIT-Interacting Motif (MIM) sequence or a sequence with at least 50% sequence identity to said MIM sequence or b) an a-syn interaction sequence or a sequence with at least 50% sequence identity to said a-syn interaction sequence, wherein the peptide that binds CHMP2B or inhibits CHMP2B-a-syn interaction by at least 50%, wherein the peptide optionally comprises one or more exogenous residues, optionally interspersed for example for one or more, optionally two cysteines.
Dependencies are inferred from the claim text.