Targeting USP11 regulation by a novel lithium-organic coordination compound improves neuropathologies and cognitive functions in Alzheimer transgenic mice.

ABSTRACT: Alzheimer's Disease (AD), as the most common neurodegenerative disease worldwide, severely impairs patients' cognitive functions. Although its exact etiology remains unclear, the abnormal aggregations of misfolded β-amyloid peptide and tau protein are considered pivotal in its pathological progression. Recent studies identify ubiquitin-specific protease 11 (USP11) as the key regulator of tau deubiquitination, exacerbating tau aggregation and AD pathology. Thereby, inhibiting USP11 function, via either blocking USP11 activity or lowering USP11 protein level, may serve as an effective therapeutic strategy against AD. Our research introduces IsoLiPro, a unique lithium isobutyrate-L-proline coordination compound, effectively lowers USP11 protein level and enhances tau ubiquitination in vitro.

SUBMITTER: Guo Y 

PROVIDER: S-EPMC11555261 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature