A splice-switching antisense oligonucleotide targeting APP reduces accumulation of α-synuclein in a mouse model of Parkinson's disease.

ABSTRACT:

Introduction

Alzheimer's disease (AD) and Parkinson's disease (PD) are neurodegenerative disorders characterized by abnormal protein aggregation, with amyloid beta (Aβ) and α-synuclein (α-syn) as key pathological markers. Increasing evidence highlights a pathological interplay between Aβ and α-syn, exacerbating neurodegeneration in both AD and PD. In this study, we evaluated the effects of reducing amyloid precursor protein (APP) processing on α-syn pathology using a splice-switching oligonucleotide (SSO) targeting APP exon 15 in Thy1-α-syn transgenic (α-syn-tg) mice.

Methods

α-syn-tg mice received systemic APP SSO treatment. Immunohistochemistry and immunoblotting assessed α-syn, phosphorylated α-syn (P-Syn), and APP C-terminal fragments (CTFs) in the cortex, hippocampus, a

SUBMITTER: Ahammad RU 

PROVIDER: S-EPMC12185244 | biostudies-literature | 2025 Apr-Jun

REPOSITORIES: biostudies-literature