Article Archive

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.

Activating V600E in BRAF is a common driver mutation in cancers of multiple tissue origins. BRAF V600E has also been implicated in neurodegeneration. The present study aims to characterize BRAF V600E on cell death and survival in three major cell types of the CNS: neurons, astrocytes, and microglia.

Aβ peptides derived from the amyloid precursor protein (APP) have been implicated in the pathogenesis of Alzheimer’s disease. However, the normal function of APP is less clear. Results demonstrate a conserved role for APP in controlling age-dependent proteostasis with plausible relevance to Alzheimer’s disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of motor function. Using a mouse model, the authors demonstrate that infection with Helicobacter pylori leads to the development of motor and cognitive signs.

Parkinson’s disease is a neurodegenerative condition characterized by large intraneuronal aggregates in the brain. It has been hypothesized that these large aggregates may form from smaller soluble protein assemblies, often termed oligomers. ASA-PD, is a new imaging method to generate large-scale α-synuclein oligomer maps in post-mortem human brain tissue.

This article focuses on the VEGFs/VEGFRs involvement in neurodegenerative diseases by reviewing the current literature on the rather complex VEGFs/VEGFRs contribution to the pathogenic mechanisms of Alzheimer’s (AD) and Parkinson’s disease (PD).

Published: Existing spatial transcriptomics techniques are either limited by capture array density or are cost-prohibitive for large-scale atlasing. Nova-ST, a dense nano-patterned spatial transcriptomics technique derived from randomly barcoded Illumina sequencing flow cells enables customized, low-cost, flexible, and high-resolution spatial profiling of large tissue sections. View original preprint.

Published: Neurosurgical targeting in nonhuman primates (NHPs) requires presurgical anatomy mapping with neuroimaging techniques (MRI, CT, PET). Given the varied tissue contrasts that these imaging techniques produce, the alignment of imaging-based coordinates to surgical apparatus can be cumbersome. The authors developed an MRI-compatible stereotaxis allowing alignment through technique-specific fiducial markers. View original preprint.

Published: Characterization of Parkinson's disease (PD) progression using real-world evidence could guide clinical trial design and identify subpopulations. This study characterizes Parkinson's progression in diverse populations. It delineates systemic divergences in the patient populations enrolled in research settings vs. patients in the real world. View original preprint. 

Genome-edited human pluripotent stem cells (hPSCs) offer the unique potential to advance the understanding of Parksion's etiology by providing disease-relevant cell types carrying patient mutations along with isogenic control cells. To facilitate this experimental approach, the authors generated a collection of cell lines harboring mutations in genes associated with Parkinson's.

In this review, the authors highlight advances in the fast-developing field of single-cell and spatial multi-omics technologies (also known as multimodal omics approaches), and the computational strategies needed to integrate information across molecular layers.

This review is the second in a series of three papers about Parkinson's disease published in the Lancet.

Increasing efforts have been made to elucidate how genetic and environmental factors interact in Parkinson's disease (PD). In the present study, the authors assessed the development of PD-like symptoms on a PD rat model overexpressing human α-synuclein at a presymptomatic age, exposed to a pro-inflammatory insult by injection of lipopolysaccharide.

Biallelic (autosomal recessive) pathogenic variants in ATP13A2 cause a form of juvenile-onset parkinsonism, termed Kufor-Rakeb syndrome. The article describes the treatment response in an individual with Kufor-Rakeb syndrome-associated psychosis.

Two papers in this issue resolve a long-standing obstacle to a “standard model” for autophagosome biogenesis in mammals.

Published: The authors identify novel transcripts from both GBA1 and GBAP1, including protein-coding transcripts that are translated in vitro and detected in proteomic data, but that lack GCase activity. View original preprint. 

Parkinson’s disease (PD) is a multisystem disorder with characteristics of a chronic inflammatory disease. To develop effective immunomodulatory interventions to combat PD, researchers need to think innovatively about the implications of orchestrated central and peripheral innate and adaptive immune responses that occur as the disease begins and progresses.