The spiking activity of the subthalamic nucleus, rather than the activity of striatal projection neurons, orchestrates basal ganglia downstream activity and output commands in health and Parkinson’s disease.
A crucial step during the mitophagy cascade involves the disassembly of connections between mitochondria and the endoplasmic reticulum via the retrotranslocation of Mfn2 tethering complexes by the Parkinson's disease genes PARKIN and PINK1, as well as the ATPase VCP/p97.
The alpha-synuclein fibril structure reported here buries residues 50-57 at the interface between its two protofilaments, suggesting that familial Parkinson's disease associated mutations in these residues lead to a structure not compatible with the one presented here.
LRRK2 G2019S knock-in mice are a genetically faithful model that recapitulates the slow disease progression of familial PD, with initial alterations to behaviour and neurotransmission providing early pathophysiological targets for neuroprotective interventions.
Striatal dopamine 2/3 receptor (D2/3R) availability is related to working memory-induced functional connectivity changes in the default mode network, and this mediates the relationship between D2/3Rs and task performance.
The high affinity α-synuclein-monomer binder AS69 converts into a strong sub-stoichiometric inhibitor of nucleation processes upon formation of the AS69-α-synuclein complex, achieving reduced aggregation in vitro and in vivo.