Two C-terminal sequence variations determine differential neurotoxicity between human and mouse α-synuclein.

ABSTRACT:

Background

α-Synuclein (aSyn) aggregation is thought to play a central role in neurodegenerative disorders termed synucleinopathies, including Parkinson's disease (PD). Mouse aSyn contains a threonine residue at position 53 that mimics the human familial PD substitution A53T, yet in contrast to A53T patients, mice show no evidence of aSyn neuropathology even after aging. Here, we studied the neurotoxicity of human A53T, mouse aSyn, and various human-mouse chimeras in cellular and in vivo models, as well as their biochemical properties relevant to aSyn pathobiology.

Methods

Primary midbrain cultures transduced with aSyn-encoding adenoviruses were analyzed immunocytochemically to determine relative dopaminergic neuron viability. Brain sections prepared from rats injected intra

SUBMITTER: Landeck N 

PROVIDER: S-EPMC7487555 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature