Generation of the iPSC line FINi002-A from a male Parkinson’s disease patient carrying compound heterozygous mutations in the PRKN gene
By Julia Julia Leonard onThis 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.
Alpha-synuclein overexpression can drive microbiome dysbiosis in mice
By Emma Sherrell onGrowing 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 shadow imaging for neuroscience
By Emma Sherrell onFluorescence 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.
Generation of locus coeruleus norepinephrine neurons from human pluripotent stem cells
By Julia Julia Leonard onCentral 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.
Circular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease
By savannah onLittle 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.
Evaluating the performance of polygenic risk profiling across diverse ancestry populations in Parkinson’s disease
By savannah onObjective: This study aims to address disparities in risk prediction by evaluating the performance of polygenic risk score (PRS) models using the 90 risk variants across 78 independent loci previously linked to Parkinson’s disease (PD) risk across seven diverse ancestry populations.
NeuroBooster Array: A genome-wide genotyping platform to study neurological disorders across diverse populations
By Devin Della Maggiora onPreprint: People envisage this valuable tool will standardize genetic studies in neurological disorders across different ancestral groups, allowing researchers to perform genetic research inclusively and at a global scale.
The non-coding GBA1 rs3115534 variant is associated with REM sleep behavior disorder in Nigerians
By Devin Della Maggiora onPreprint: The authors studied 709 persons with PD, which show that the non-coding GBA1 rs3115534 risk variant is associated with increased RBD symptomatology in Nigerians with PD. Further research is required to assess association with polysomnography-defined RBD.
State-dependent GABAergic regulation of striatal spiny projection neuron excitability
By Devin Della Maggiora onOur 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 intrastriatal GABAergic circuits.
Mutations in GPNMB associated with Amyloid cutis dyschromica alter intracellular trafficking and processing of GPNMB
By Julia Julia Leonard onPreprint: 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.
Polyamines in Parkinson’s Disease: Balancing Between Neurotoxicity and Neuroprotection
By Emma Sherrell onPublished: 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.
Lyso-IP: Uncovering Pathogenic Mechanisms of Lysosomal Dysfunction
By Emma Sherrell onPublished: Future applications of rapid lysosomal isolation techniques are likely to greatly enhance our understanding of lysosomal dysfunction in rare and common neurodegeneration causes.
Modelling human brain-wide pigmentation in rodents recapitulates age-related multisystem neurodegenerative deficits
By savannah onIn parallel to progressive human-like neuromelanin pigmentation, these animals display age-related neuronal dysfunction and degeneration affecting numerous brain circuits and body tissues, linked to motor and non-motor deficits, reminiscent of early neurodegenerative stages. This model may open new research avenues in the field of brain aging and neurodegeneration.
Adult-specific Reelin expression alters striatal neuronal organization: implications for neuropsychiatric disorders
By savannah onThe authors increased Reelin levels might modulate the numbers of striatal interneurons and the density of the nigrostriatal dopaminergic projections, suggesting that these changes may be involved in the protection of Reelin against neuropsychiatric disorders. View original preprint.
Is Gauchian genotyping of GBA1 variants reliable?
By Emma Sherrell onPreprint: The authors evaluated Gauchian in 90 Sanger-sequenced patients with GD and five GBA1 heterozygotes using the software tool Gauchian to identify GBA1 variants from whole genome sequencing. While Gauchian genotyped most patients correctly, this limits Gauchian's utility in variant screening and precluding its use in diagnostics.
Population fraction of Parkinson’s disease attributable to preventable risk factors
By Emma Sherrell onPublished: The team identified repeated blows to head in sports/combat as a potential new risk factor. 23% of PD cases in females were attributable to pesticides/herbicides exposure, and 30% of PD in males were attributable to pesticides/herbicides, military-related chemical exposures, and repeated blows to the head, and therefore could have potentially been prevented. View original preprint.
PyRates—A code-generation tool for modeling dynamical systems in biology and beyond
By Emma Sherrell onPublished: The main purpose of the paper is to demonstrate how these three tools can support the computational/mathematical modeling of neural systems with a variety of numerical methods that are well tested and documented. Thus, the authors present a powerful tool kit for computational/mathematical approaches to studying the dynamics and functions of complex neural systems such as the basal ganglia. View original preprint.
RASP: Optimal single fluorescent puncta detection in complex cellular backgrounds
By savannah onPreprint: This sensitive, computationally efficient approach enables fluorescent puncta and cellular features to be distinguished in cellular and tissue environments with a sensitivity down to the level of the single protein.
Disrupted sleep-wake regulation in the MCI-Park mouse model of Parkinson’s disease
By Emma Sherrell onPublished: To understand PD-associated sleep-wake abnormalities, a new progressive model of PD - the MCI-Park mouse - was studied. Near the transition to the parkinsonian state, these mice exhibited significantly altered sleep-wake regulation, including increased wakefulness, decreased non-rapid eye movement (NREM) sleep, increased sleep fragmentation, reduced rapid eye movement (REM) sleep, and altered EEG activity patterns. View original preprint.
Rethinking the network determinants of motor disability in Parkinson’s disease
By Emma Sherrell onWhile the basal ganglia circuit model underpinning the notion that striatal dopamine (DA) depletion was the critical determinant of network pathophysiology underlying the motor symptoms of Parkinson’s disease, the hypothesis itself has never been directly tested. It is time for a new model of the network determinants of motor disability in PD.