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Proportion and distribution of neurotransmitter-defined cell types in the ventral tegmental area and substantia nigra pars compacta
onThe 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.
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GLP-1 receptor agonism ameliorates Parkinson’s disease through 1 modulation of neuronal insulin signalling and glial suppression
onNeuronal 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.
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Adoptive transfer of mitochondrial antigen-specific CD8+ T-cells in mice causes parkinsonism and compromises the dopamine system
onThe 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.
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LRRK2 G2019S mutation suppresses differentiation of Th9 and Treg cells via JAK/STAT3
onThe 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.
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Deep sequencing of proteotoxicity modifier genes uncovers a Presenilin-2/beta-amyloid-actin genetic risk module shared among alpha-synucleinopathies
onConventional 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.
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Alpha-synuclein aggregates trigger anti-viral immune pathways and RNA editing in human astrocytes
onParkinson'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.
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Dopamine neuron activity encodes the length of upcoming contralateral movement sequences
onThe relationship between the activity of dopaminergic neurons (DANs) and the length of movement sequences is unknown. The authors imaged the activity of SNc DANs in mice. Results indicate that movement-initiation DANs encode more than a general motivation signal and invigorate aspects of contralateral movements. View original preprint.
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