Collaborative Research Network Archive

In this study, the authors utilized human and murine neuronal lines, stem cell-derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA, are components of a single gene regulatory pathway.

The authors identified p53-mediated apoptotic cell death as a major contributor to dopamine neuron loss and uncovered a causal link of TNFa-NFκB signaling in limiting cell survival.

Phosphorylation of αsyn at serine 129 (PSER129) was considered rare in the healthy human brain but is enriched in pathological αsyn aggregates and is used as a marker for disease inclusions. Recent observations challenge this assumption. The authors investigated conditions under which PSER129 could be detected in the mammalian brain.

Here, the authors demonstrate that loss of nigral dopaminergic neurons, loss of putamenal dopaminergic innervation, and loss of the tyrosine hydroxylase-phenotype in the substantia nigra and putamen occur equally in mild motor deficit groups with and without nigral alpha-synuclein aggregates.

This study assesses the complex connections between α-synucleinopathies, gut-brain connectivity, and the emergence of non-motor phenotypes.

In this review, the authors revisit the history of gut-brain interactions in science and medicine, which dates back to at least the eighteenth century, and outline how concepts in this field have shifted and evolved across eras.

The authors developed scNAT, a deep learning method that integrates paired scRNA-seq and scTCR-seq data to represent data in a unified latent space for downstream analysis.

For unclear reasons, PD patients with certain GBA1 mutations (GBA-PD) have a more aggressive clinical progression. The authors tested the two hypotheses for why this occurs; that GBA1 mutations promote αsyn spread or drive the generation of highly pathogenic αsyn polymorphs (i.e., strains).

The authors show that Parvalbumin interneurons that are inhibitory regulators of movement also lose primary cilia.

Parkinson’s disease-associated, activating mutations in LRRK2 block primary cilia formation, decreasing the production of neuroprotective factors that support dopaminergic neuron viability. The authors show that pathogenic LRRK2-driven cilia loss is reversible in post-mitotic neurons and astrocytes.