Expression of human A53T alpha-synuclein without endogenous rat alpha-synuclein fails to elicit Parkinson's disease-related phenotypes in a novel humanized rat model.

ABSTRACT: Alpha-synuclein (aSyn) is linked to Parkinson's disease (PD) through SNCA genetic mutations, phosphorylated aSyn in Lewy bodies and Lewy neurites, and most recently through evidence of aSyn aggregation in patient spinal fluid using the aSyn seed amplification assay. Therefore, understanding the biology of this protein and developing therapeutic interventions targeting pathological processing of aSyn are a key area of focus for novel treatments to slow or stop PD. Reliable preclinical models are imperative for these efforts. To this end, we developed a novel model using CRISPR/Cas9 to humanize the regions surrounding the naturally occurring threonine 53 amino acid in the Sprague Dawley rat to generate a humanized A53T aSyn rat model (aSyn A53T KI). We also generated an Snca knockout (aSyn K

SUBMITTER: Polinski NK 

PROVIDER: S-EPMC12334032 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature