Neural heterogeneity controls computations in spiking neural networks
By savannah onPublished: The authors want to understand how neural heterogeneity affect macroscopic neural dynamics and contribute to neurodynamic functions. Here, the authors study the macroscopic dynamics of networks of heterogeneous Izhikevich neurons. Their analysis suggests that the level of heterogeneity of inhibitory populations controls resonance and hysteresis properties of systems of coupled excitatory and inhibitory neurons. View original preprint.
Temporal landscape of mitochondrial proteostasis governed by the UPRmt
By savannah onPreprint: Breakdown of mitochondrial proteostasis activates quality control pathways including the mitochondrial unfolded protein response (UPRmt) and PINK1/Parkin mitophagy. The authors developed a functional proteomics framework, termed MitoPQ (Mitochondrial Proteostasis Quantification), to dissect the UPRmts role in maintaining proteostasis during stress.
GRN mutations are associated with Lewy body dementia
By savannah onPublished: This paper sought to assess a Lewy body dementia case control cohort for pathogenic variants in GRN and identify mutations among patients.
Assessing the relationship between monoallelic PRKN mutations and Parkinson’s risk
By savannah onPublished: This paper examines the role of heterozygous Parkin mutations in three large independent case control cohorts.
Analysis of Y chromosome haplogroups in Parkinson’s disease
By savannah onPublished: This paper explores the role of the Y chromosome in PD by analyzing whole genome sequencing data from multiple sources.
Deficiency in endocannabinoid synthase 1 DAGLB contributes to Parkinson’s disease and dopaminergic neuron dysfunction
By savannah onPublished: In this paper, the authors linked multiple homozygous loss-of-function mutations in the endocannabinoid 2-AG synthase diacylglcerol lipase beta (DAGLB) to early onset autosomal recessive PD using genetic knockdown and pharmacological inhibition of 2-AG in substantia nigra dopaminergic neurons.
Replication assessment of NUS1 variants in Parkinson’s disease
By savannah onPublished: NUS1 was recently associated with PD in the Chinese population. Here, the authors used large-scale PD case-control cohorts to assess NUS1 variants in individuals of European ancestry.
17q21.31 sub-haplotypes underlying H1-associated risk for Parkinson’s disease are associated with LRRC37A/2 expression in astrocytes
By savannah onPublished: This paper examines the H1 haplotype of the MAPT 17q.21.31 locus to better understand its contribution to PD. The authors found three novel H1 sub-haplotype blocks across the 17q.21.31 locus that is associated with PD risk.
The Parkinson’s disease protein alpha-synuclein is a direct modulator of RNA processing-bodies and mRNA stability
By savannah onPublished: The authors explored the molecular roles of alpha-synuclein and found that it directly modulates processing bodies (P-bodies), organelles that are involved in mRNA turnover and storage.
Heterozygous PRKN mutations are common but do not increase the risk of Parkinson’s disease
By savannah onPublished: In this paper, the authors completed a comprehensive assessment of Parkin mutations at population-scale to understand the prevalence of heterozygous Parkin mutations.
Joint modeling study identifies blood-based transcripts link to cognitive decline in Parkinson’s disease
By savannah onPublished: In this paper, the authors sought to find transcriptome-wide biomarkers in blood that could predict cognitive decline and identify PD patients at risk of developing cognitive impairments. Using transcriptome-wide longitudinal gene expression modeling analysis, they identified blood-based five transcripts associated with cognitive decline.
Multi-platform proteomic analysis of Alzheimer’s disease cerebrospinal fluid and plasma reveals network biomarkers associated with proteostasis and the matrisome
By savannah onPreprint: The authors analyzed cerebrospinal fluid and plasma from Alzheimer's patients using various assays to understand which protein markers in these biofluids may be reliable biomarkers for AD pathophysiology.
Melanocortin 1 receptor activation protects against alpha-synuclein pathologies in models of Parkinson’s disease
By savannah onPublication: The authors previously showed that MC1R signaling can facilitate nigrostriatal dopaminergic neuron survival. The present study investigates the neuroprotective potential of MC1R against neurotoxicity induced by alpha-synuclein, a key player in PD genetics and pathogenesis. View original preprint.
Loss of tau expression attenuates neurodegeneration associated with α-synucleinopathy
By savannah onPublication: The role of tau in the development of αS pathology and subsequent neuronal dysfunction has been controversial. Herein, the authors examine the role of tau in the onset and progression of αS pathology using a transgenic mouse model of α-synucleinopathy lacking mouse tau expression. View original preprint.
Sphingolipid changes in Parkinson L444P GBA mutation fibroblasts promote α-synuclein aggregation
By savannah onPublication: In this study, the lipid membrane composition of fibroblasts isolated from control subjects, patients with idiopathic Parkinson's disease and Parkinson's disease patients carrying the L444P GBA mutation (PD-GBA) was assayed using shotgun lipidomics. Findings suggest that L44P GBA mutations have a distinctly altered membrane lipid profile. View original preprint.
Motor learning selectively strengthens cortical and striatal synapses of motor engram neurons
By savannah onPublication: Learning and consolidating new motor skills require plasticity in the motor cortex and striatum, two key motor regions of the brain. However, how neurons undergo synaptic changes and become recruited during motor learning to form a memory remains unknown. Here the authors identify M1 engram neurons important for memory.
A prebiotic diet modulates microglial states and motor deficits in α-synuclein overexpressing mice
By savannah onPublication: The gut microbiome is altered in PD and may impact motor and GI symptoms as indicated by animal studies, although mechanisms of gut-brain interactions remain incompletely defined. Here, the authors investigated whether a fiber-rich diet influences microglial function in α-synuclein overexpressing (ASO) mice, a preclinical model with PD-like symptoms and pathology. View original preprint.
R1441C and G2019S LRRK2 knock-in mice have distinct striatal molecular, physiological, and behavioral alterations
By savannah onPublication: LRRK2 mutations are closely associated with PD. Convergent evidence suggests that LRRK2 regulates striatal function. Here, by using knock-in mouse lines expressing the two most common LRRK2 pathogenic mutations – G2019S and R1441C – the authors investigated how LRRK2 mutations altered striatal physiology. View original preprint.
Regulatory imbalance between LRRK2 kinase, PPM1H phosphatase, and ARF6 GTPase disrupts the axonal transport of autophagosomes
By savannah onPreprint: Gain-of-function mutations in the LRRK2 gene cause Parkinson's disease (PD), increasing phosphorylation of RAB GTPases through hyperactive kinase activity. The authors found that LRRK2-hyperphosphorylated RABs disrupt the axonal transport of autophagosomes by perturbing the coordinated regulation of cytoplasmic dynein and kinesin motors.
Genome-wide Analysis of Motor Progression in Parkinson Disease
By savannah onPublished: In this article, the authors explored whether there are genetic variants that explain variability in the motor progression found in Parkinson’s in clinical cohorts. They performed a large study genome scan looking at the influence of genetic variation on motor progression and the worsening of motor capabilities among thousands of Parkinson's patients. View original preprint.