Dataset Information


Tau knockout exacerbates degeneration of parvalbumin-positive neurons in substantia nigra pars reticulata in Parkinson's disease-related α-synuclein A53T mice.

ABSTRACT: α-Synuclein (α-syn)-induced neurotoxicity has been generally accepted as a key step in the pathogenesis of Parkinson's disease (PD). Microtubule-associated protein tau, which is considered second only to α-syn, has been repeatedly linked with PD in association studies. However, the underlying interaction between these two PD-related proteins in vivo remains unclear. To investigate how the expression of tau affects α-syn-induced neurodegeneration in vivo, we generated triple transgenic mice that overexpressed α-syn A53T mutation in the midbrain dopaminergic neurons (mDANs) with different expression levels of tau. Here, we found that tau had no significant effect on the A53T α-syn-mediated mDANs degeneration. However, tau knockout could modestly promote the formation of α-syn aggregates, accelerate the severe and progressive degeneration of parvalbumin-positive (PV+) neurons in substantia nigra pars reticulata (SNR), accompanied with anxiety-like behavior in aged PD-related α-syn A53T mice. The mechanisms may be associated with A53T α-syn-mediated specifically successive impairment of N-methyl-d-aspartate receptor subunit 2B (NR2B), postsynaptic density-95 (PSD-95) and microtubule-associated protein 1A (MAP1A) in PV+ neurons. Our study indicates that MAP1A may play a beneficial role in preserving the survival of PV+ neurons, and that inhibition of the impairment of NR2B/PSD-95/MAP1A pathway, may be a novel and preferential option to ameliorate α-syn-induced neurodegeneration.

PROVIDER: S-EPMC8353962 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC8239288 | BioStudies
| S-EPMC7289511 | BioStudies
| S-EPMC8748802 | BioStudies
| S-EPMC124407 | BioStudies
| S-EPMC8161267 | BioStudies
| S-EPMC2812632 | BioStudies
| S-EPMC8001805 | BioStudies
2019-01-01 | S-EPMC6597809 | BioStudies
| S-EPMC3731353 | BioStudies
| S-EPMC7115172 | BioStudies