Neuronal presentation of antigen and its possible role in Parkinson’s disease
By savannah onReview: Patients with Parkinson's disease and other synucleinopathies often exhibit autoimmune features, including CD4+ and some CD8+ T lymphocytes that recognize epitopes derived from alpha-synuclein. This article reviews the literature on neuronal antigen presentation and its potential role in PD.
Induced pluripotent stem cells: a tool for modeling Parkinson’s disease
By savannah onReview: Recent advances in induced pluripotent stem cell (iPSC) technology have made it possible to generate patient-derived DA neuronal cell culture and organoid models of PD. These models have contributed to understanding disease mechanisms and the identification of novel targets and therapeutic candidates.
Targeting cellular senescence with senotherapeutics: senolytics and senomorphics
By savannah onReview: This article reviews the current state of the development of senolytics and senomorphics for the treatment of age-related diseases and disorders and extension of healthy longevity. In addition, the challenges of documenting senolytic and senomorphic activity in pre-clinical models and the current state of the clinical application of the different senotherapeutics are discussed.
State-of-the-art review of the clinical research on menopause and hormone replacement therapy association with Parkinson’s disease: what meta-analysis studies cannot tell us
By savannah onReview: This article provides a unified overview of the clinical literature on the influence of menopause and ovarian hormones on Parkinson’s disease. We highlight the possible sources of conflicting evidence and gather considerations for future observational clinical studies that aim to explore the neurological impact of menopause-related features in Parkinson’s disease.
Molecular heterogeneity in the substantia nigra: a roadmap for understanding PD motor pathophysiology
By savannah onReview: This article discusses the existing knowledge of DA neuron subtypes and attempts to provide a roadmap for how their distinctive properties can provide novel insights into the motor symptoms of Parkinson's disease (PD).
Sst+ GPi output neurons provide direct feedback to key nodes of the basal ganglia and drive behavioral flexibility
By savannah onPreprint: The GPi-LHb pathway is the main output of the basal ganglia suggested to shape motivated behaviors. Here, the authors propose that GPi Sst+ neurons drive behavioral flexibility through a direct feedback signal to balance the activity of key nodes in the basal ganglia.
Macroscopic dynamics of neural networks with heterogeneous spiking thresholds
By savannah onPublished: The authors develop a new computational model to represent different neuron types and spiking dynamics. The model is comprised of biophysical state variables and parameters, incorporates realistic spike resetting conditions, and accounts for heterogeneity in neural spiking thresholds. These features allow for a broad applicability of the model as well as for a direct comparison to experimental data. View original preprint.
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.