report Archive

Mutations in the lysosomal enzyme β-glucocerebrosidase (GCase), which cause Gaucher's disease, are the most frequent genetic risk factor for Parkinson’s disease (PD). Here, the authors employed global proteomic and single-cell genomic approaches in stable cell lines as well as induced pluripotent stem cell (iPSC)-derived neurons and midbrain organoids to dissect the mechanisms underlying GCase-related neurodegeneration.

A bioinformatics approach was taken to investigate the proteome of the NSL complex, to unpick its relevance to PD progression. The authors’ data points to NSL complex members OGT and WDR5 as key drivers of this increased PD association. These findings strengthen a role for mitochondrial quality control in both familial and sporadic disease.

These results demonstrate the remarkable capacity for achieving functional and anatomically precise reconstruction of long-distance circuitry in the adult brain by matching appropriate growth-factor signaling to grafting of specific cell types.

This Blueprint presents initial findings on how ASAP’s approach to open science has solidified and evolved over its first three years, data and metrics on progress, and CC-BY versions of assets that can be adopted and adapted by others. ASAP plans to update the Blueprint with new findings and assets on a regular basis.

The authors conclude that basal ganglia neurons fire in recognizable sequences of ISIs, whose incidence is influenced by the induction of parkinsonism.

This review focuses on key advances in generating new neurons through in situ neuronal reprogramming, which is tied to fundamental questions regarding adult neurogenesis, cell source, and mechanisms for neuronal reprogramming, as well as the ability of new neurons to integrate into the existing circuitry.