Topic: dopaminergic neuron degeneration

Parkinson’s disease (PD) is characterised by midbrain dopaminergic neuron degeneration resulting from intraneuronal a-synuclein (aSyn) accumulation. Adeno-associated virus (AAV)-mediated delivery of neurotrophic factors (NTFs), including GDNF, has been tested in clinical trials and has potential to be used as disease-modifying therapy for PD. We have previously shown that the NTF growth/differentiation factor 5 (GDF5) exerts neuroprotective effects after intranigral delivery in an aSyn rat model of PD. Here we examined whether delivery of GDF5 and GDNF to the striatum (putamen), a more clinica

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by midbrain dopaminergic neuron degeneration and intracellular a-synuclein (aSyn) accumulation. Here we show that AAV-shRNA-mediated inhibition of HDAC5 protected against aSyn-induced neurodegeneration in vitro and in vivo. We also show that AAV-mediated overexpression of aSyn induces HDAC5 nuclear accumulation in dopaminergic neurons in the rat substantia nigra in vivo, and in SH-SY5Y cells in vitro. To investigate the nuclear HDAC5 complex induced by aSyn, we used a co-immunoprecipitation proteomics approach t

The neurodegenerative process in Parkinson’s disease involves exacerbated inflammation with the participation of astrocytes. The P2Y1 receptor (P2Y1R) is a purinergic receptor predominantly expressed in astrocytes, regulating their activity, proliferation, and glutamate release. Therefore, our investigation explores whether the P2Y1R contributes to dopaminergic neuron degeneration, potentially via astrocytic involvement. To study dopaminergic degeneration, we injected 9 µg 6-hydroxydopamine into the right striatum (STR) of male Sprague-Dawley rats aged 6-8 weeks (ethical approval: 167/2019). D