公开(公告)号：US20240207359A1

公开(公告)日：2024-06-27

申请号：US18421775

申请日：2024-01-24

Applicant: UNIVERSITY OF SOUTH FLORIDA

Inventor： Jung A. WOO ,  Stephen Bryant LIGGETT ,  David E. KANG ,  Yu CHEN ,  Eric LEWANDOWSKI

IPC: A61K38/17 ,  A61K31/42 ,  A61K31/437 ,  A61K31/496 ,  A61P25/28

CPC classification number: A61K38/1709 ,  A61K31/42 ,  A61K31/437 ,  A61K31/496 ,  A61P25/28

Abstract: As disclosed herein, β-arrestin1 and β-arrestin2 levels are highly elevated in brains of FTLD-tau patients suggesting that both β-arrestin1 and β-arrestin2 are elevated in the brains of patients with AD and FLTD. The current work also shows that when β-arrestin2 is overexpressed, tau levels become elevated. The data indicate that β-arrestin2 reduces tau clearance by impairing p62-mediated autophagy, a role carried out by the oligomerized form of β-arrestin2. Therefore, disclosed herein are β-arrestin oligomerization inhibitors that can be used to prevent β-arrestin oligomerization and therefore the accumulation of tau in cells, i.e. tauopathy. Also disclosed are methods of treating a tauopathy in a subject that involve administering to the subject a therapeutically effective amount of a β-arrestin oligomerization inhibitor disclosed herein.

公开(公告)号：US20230116783A1

公开(公告)日：2023-04-13

申请号：US17798041

申请日：2021-02-08

Applicant: UNIVERSITY OF SOUTH FLORIDA

Inventor： Jung A. WOO ,  Stephen Bryant LIGGETT ,  David E. KANG ,  Yu CHEN ,  Eric LEWANDOWSKI

IPC: A61K38/17 ,  A61P25/28 ,  A61K31/437 ,  A61K31/496 ,  A61K31/42

Abstract: As disclosed herein, β-arrestin1 and β-arrestin2 levels are highly elevated in brains of FTLD-tau patients suggesting that both β-arrestin1 and β-arrestin2 are elevated in the brains of patients with AD and FLTD. The current work also shows that when β-arrestin2 is overexpressed, tau levels become elevated. The data indicate that β-arrestin2 reduces tau clearance by impairing p62-mediated autophagy, a role carried out by the oligomerized form of β-arrestin2. Therefore, disclosed herein are β-arrestin oligomerization inhibitors that can be used to prevent β-arrestin oligomerization and therefore the accumulation of tau in cells, i.e. tauopathy. Also disclosed are methods of treating a tauopathy in a subject that involve administering to the subject a therapeutically effective amount of a β-arrestin oligomerization inhibitor disclosed herein.