HDAC11 displays neuropathological alterations and offers as a novel drug target for Alzheimer's disease.

ABSTRACT:

Introduction

Alzheimer's disease (AD) is characterized by amyloid pathology and neuroinflammation, leading to cognitive decline. Targeting histone deacetylase-11 (HDAC11) offers a novel therapeutic strategy due to its role in immune regulation.

Methods

We conducted neuropathological analyses on human AD post mortem brain tissues and 5xFAD transgenic mice. We developed PB94, a brain-permeable HDAC11-selective inhibitor, and assessed its effects using live-animal imaging and behavioral studies.

Results

HDAC11 was significantly upregulated in AD brains, correlating with amyloid pathology and neuroinflammatory markers. PB94 treatment reduced amyloid burden and neuroinflammation, improving cognitive function in 5xFAD mice.

Discussion

Our findings highlight HDAC11 as

SUBMITTER: Bai P 

PROVIDER: S-EPMC11923381 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature