Collaborative Research Network Archive

Not all persons with PD have a dysbiotic microbiome, and not all dysbiotic PD microbiomes have the same features. The authors have developed an intuitive and easily modifiable method to identify the optimal candidates for microbiome-based clinical trials, and subsequently, for treatments that are personalized for each individual's dysbiotic features.

The relative distributions and proportions of neurotransmitter-defined cell types across VTA and SNc have remained unclear. The data shown here complement recent single-cell RNAseq studies and support a more diverse landscape of neurotransmitter-defined cell types in VTA and SNc.

Neuronal insulin resistance is linked to the pathogenesis of Parkinson's disease through unclear, but potentially targetable, mechanisms. The authors delineated neuronal and glial mechanisms of insulin resistance and glucagon-like 1 peptide (GLP-1) receptor agonism in human iPSC models of synucleinopathy.

The degeneration of dopamine neurons in the ventral midbrain is linked to the development of motor symptoms in Parkinson's disease (PD). Evidence suggests that neuroinflammation and mitochondrial dysfunction drive neurodegenerative mechanisms in PD. Results provide evidence for mitochondrial-specific CD8+ T cell infiltration in the brain in driving PD-like pathology.

The Leucine-rich repeat kinase-2 (LRRK2) G2019S mutation is one of the well-recognized genetic risk factors in Parkinson's disease (PD). Increased LRRK2 activity was also observed in immune cells from PD patients. The authors generated and characterized a new T cell receptor (TCR) transgenic mouse strain bearing LRRK2 G2019S knock-in mutation.

Conventional genetic analyses are underpowered to address whether neurodegenerative diseases linked to misfolding of the same protein share genetic risk drivers or whether different protein-aggregation pathologies in neurodegeneration are mechanistically related. The authors study patients based on protein aggregation phenotype to detect variants in a targeted set of genes.

Parkinson's disease is a neurodegenerative disease characterized by a proteinopathy with marked astrogliosis. To investigate how a proteinopathy may induce a reactive astrocyte state, and the consequence of reactive astrocytic states on neurons, the authors generated hiPSC-derived astrocytes, neurons, and co-cultures and exposed them to small soluble alpha-synuclein aggregates.

Published: Dopamine neurons (DANs) in the substantia nigra pars compacta (SNc) have been related to movement vigor, and loss of these neurons leads to bradykinesia in Parkinson’s disease. Here the authors investigate whether DANs encode a general motivation signal or modulate movement kinematics. View original preprint.