Article Archive

Neuromuscular disorders caused by dysfunction of the mitochondrial respiratory chain are common, severe, and untreatable. The authors recovered a number of mitochondrial genes, including electron transport chain components, in a large forward genetic screen for mutations causing age-related neurodegeneration in the context of proteostasis dysfunction.

Published: Activating LRRK2 mutations causes Parkinson's disease. Previously, work showed that cholinergic interneurons and astrocytes lose primary cilia in LRRK2 mutant mice. Here, the data strongly suggest that loss of cilia in specific striatal cell types decreases neuroprotection for dopamine neurons in mice and human Parkinson's disease. View original preprint.

An open-source behavioral platform and software solution for studying fine motor skills in mice performing reach-to-grasp tasks. The behavioral platform uses readily available and 3D-printed components and was designed to be affordable and universally reproducible.

Probing how human neural networks operate is hindered by the lack of reliable human neural tissues amenable to the dynamic functional assessment of neural circuits. Team Scherzer developed a 3D bioprinting platform to assemble tissues with defined human neural cell types in a desired dimension using a commercial bioprinter.

Dedicated assembly factors orchestrate the stepwise production of molecular machines, including the 28-subunit proteasome core particle (CP) that mediates protein degradation. This article presents cryo-EM reconstructions of seven recombinant human subcomplexes that visualize all five chaperones and the three active site propeptides across a wide swath of the assembly pathway. View original preprint.

Aging can be associated with the accumulation of polyglucosan bodies (PGBs). While PGBs have a detrimental effect on cognition, the underlying mechanism and clinical relevance of age-related PGB accumulation remain unknown. Here, the authors investigated the genetic basis and functional impact of age-related PGB accumulation in mice.

Published: Mutations in gene encoding tau cause autosomal dominant forms of frontotemporal dementia. Prior models of frontotemporal dementia replicate features of the disease but do not recreate the genetic context. This article presents a genetic model of tauopathy, which recapitulates the genetic context and phenotypic features of the disease. View original preprint.

Emerging evidence suggests that non-coding RNAs (ncRNAs) contribute to molecular events underlying progressive neuronal degeneration. This review discusses recent literature focused on the role of RNA-based mechanisms involved in different aspects of neuronal pathology in Parkinson’s disease and synucleinopathy models.

This article describes the generation of the iPSC line FINi002-A from a male Parkinson's disease patient carrying compound heterozygous mutations in the PRKN gene.

Growing evidence indicates that persons living with Parkinson's disease (PD) have a unique composition of indigenous gut microbes. Here, the authors used a transgenic mouse strain, which overexpress wild-type human α-syn to test how the gut microbiome composition responds in this model of PD pathology during aging.

Fluorescence microscopy remains a widely applied experimental approaches in neuroscience and beyond and is continuously evolving to make it easier and more versatile. This review highlights the inherent limitations of fluorescence microscopy and conventional labeling and summarizes the pros and cons of recent shadow imaging approaches.

Central norepinephrine (NE) neurons, located mainly in the locus coeruleus (LC), are implicated in diverse psychiatric and neurodegenerative diseases and are an emerging target for drug discovery. To facilitate their study, the authors developed a method to generate 40–60% human LC-NE neurons from human pluripotent stem cells.

Little is known about circular RNAs (circRNAs) in specific brain cells and human neuropsychiatric disease. This study shows that circular RNAs in the human brain are tailored to neuron identity and implicate circRNA-regulated synaptic specialization in neuropsychiatric diseases.

Published: The results demonstrate that GABAARs can work in concert with iGluRs to excite adult SPNs when they are in the resting down-state, suggesting that their inhibitory role is limited to brief periods near spike threshold. This state-dependence calls for a reformulation of the role of intrastriatal GABAergic circuits. View original preprint.

Preprint: Amyloid cutis dyschromica (ACD) is a rare skin condition characterized by focal areas of hyperpigmentation with hypopigm. This work highlights previously undescribed cellular characteristics of GPNMB missense mutations implicated in ACD and helps to better inform the clinically observed phenotypes, as well as underscore GPNMB’s role at melanosomes.

Published: The authors formulate outstanding research questions regarding the role of polyamines in PD, their potential as PD biomarkers, and possible therapeutic strategies for PD targeting polyamine homeostasis.

Published: Future applications of rapid lysosomal isolation techniques are likely to greatly enhance our understanding of lysosomal dysfunction in rare and common neurodegeneration causes.