Reply to: Is Gauchian genotyping of GBA1 variants reliable?
By onSummarizing a study by N. Tayebi et al. in Communications Biology, published in 2025.
Neuromelanin and selective neuronal vulnerability to Parkinson’s disease
By onNeuromelanine (NM), a pigment in human catecholamine neurons, plays a crucial role in PD. We review the development of NM in dopamine versus noradrenaline neurons and focus on previously overlooked cellular organelles in NM format and function.
Article: PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection
By onPINK1 KO mice show PD-like symptoms post intestinal infections, with myeloid cells dysregulation and T cell response early after infection. PINK1 plays a key role in gut immune functions linked to early PD mechanisms.
The bridge-like lipid transport protein VPS13C/PARK23 mediates ER-lysosome contacts upon lysosome damage
By onGenetic studies link lysosome dysfunction to Parkinson's disease. VPS13C, a PD gene, relocates to damaged lysosomes, aiding in membrane repair. This process involves Rab7 and suggests early lipid transport as a protective response.
Mitophagy in Neurons: Mechanisms Regulating Mitochondrial Turnover and Neuronal Homeostasis
By onAuthors discuss the current understanding of mitophagy mechanisms operating in neurons to govern mitochondrial homeostasis and summarize progress on our understanding of the links between mitophagic dysfunction and neurodegeneration.
Development of a simplified smell test to identify Parkinson’s disease using multiple cohorts, machine learning and item response theory
By onReduced olfaction is a common feature of typical Parkinson disease (PD) and dementia with Lewy bodies (DLB). We have created a simplified smell test based on seven specific odorants that can distinguish PD/DLB patients from healthy controls.
Leveraging animal models to understand non-motor symptoms of Parkinson’s disease
By onParkinson's disease diagnosis focuses on motor symptoms, but non-motor symptoms like cognitive issues and sleep disorders significantly affect patients. Research on non-motor signs in animals aims to improve understanding of the disease.
Comparative analysis of AAV serotypes for transduction of olfactory sensory neurons
By onThis study compared the efficacy and selectivity of 11 different AAV serotypes for the efficient and selective transduction of murine olfactory sensory neurons in vivo. The findings inform research approaches and gene therapy based initiatives.
Advances in mitophagy initiation mechanisms
By onThis review will cover recent advances in our understanding of how mitophagy is initiated, and by doing so reveal the mechanistic plasticity of how autophagosome formation can begin.
Current safety recommendations for handling mouse and human αsynuclein pre-formed fibrils
By onThe paper outlines best practices in conducting research with α-synuclein fibrils. We highlight steps in which extra precautions should be taken and how to minimize exposure and potential risk associated with use of PFFs in scientific research.
Lewy body diseases and the gut
By onGI involvement in Lewy body diseases may start with ⍺-synuclein in the gut spreading to the brain. Gut microbiome, immune system, and toxins play roles. These connections could lead to new therapies targeting the gut-brain axis for disease treatment.
A RAB7A Phosphoswitch Coordinates Rubicon Homology Protein Regulation of PINK1/Parkin-Dependent Mitophagy
By onPublished: Structural and functional data support a model in which the TBK1-dependent phosphorylation of RAB7A serves as a switch, promoting mitophagy by relieving Rubicon inhibition and favoring Pacer activation. View original preprint.
Adult-specific Reelin expression alters striatal neuronal organization: implications for neuropsychiatric disorders
By onReelin 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.
A data-driven single-cell and spatial transcriptomic map of the human prefrontal cortex
By onA data-driven molecular map of the DLPFC reveals distinct spatial domains and cell populations, offering insights into neuropsychiatric disorders. The study provides a roadmap for implementing spatial clustering approaches in the human brain.
Integrated multi-cohort analysis of the Parkinson’s disease gut metagenome
By onThe authors perform metagenomic sequencing of multiple geographically-disparate cohorts and find that stereotypic changes in the functional metabolic potential of the gut microbiome are a consistent feature of PD.
A prebiotic diet modulates microglial states and motor deficits in α-synuclein overexpressing mice
By onWhat should Parkinson's Disease patients eat? This study shows that dietary fiber impacts gut microbes and immune cells in the brain of a mouse model of Parkinson's.
Nicotine-Mediated Rescue of α-Synuclein Toxicity Requires Synaptic Vesicle Glycoprotein 2 in Drosophila
By onBackground: Parkinson's disease (PD) is characterized by α-synuclein aggregation and loss of dopamine neurons. Risk of PD arises due to a combination of genetic and environmental factors, which may interact, termed gene-environment (G×E) interactions. An inverse association between smoking and the risk of PD is well established, and a previous genome-wide G×E interaction study identified genetic variation in the synaptic-vesicle glycoprotein 2C (SV2C) locus as an important mediator of the degree to which smoking is inversely associated with PD. Objective: We sought to determine the mechanism of the smoking-SV2C interaction in a Drosophila model of PD. Methods: Flies expressing human α-synuclein in all neurons develop the hallmarks of PD, including motor dysfunction, loss of dopaminergic (DA) neurons, and formation of α-synuclein inclusions. We assessed the effects of increasing doses of nicotine on these parameters of neurodegeneration, in the presence or absence of knockdown of two Drosophila orthologues of SV2, hereafter referred to as SV2L1 and SV2L2. Results: The α-synuclein-expressing flies treated with nicotine had improved locomotion, DA neuron counts, and α-synuclein aggregation. However, in α-synuclein-expressing flies in which SV2L1 and SV2L2 were knocked down, nicotine failed to rescue neurodegeneration. Conclusions: This work confirms a G×E interaction between nicotine and SV2, defines a role for this interaction in α-synuclein proteostasis, and suggests that future clinical trials on nicotine should consider genetic variation in SV2C. Furthermore, this provides proof of concept that our model can be used for the mechanistic study of G×E, paving the way for the investigation of additional G×E interactions or the identification of novel G×E. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
RAB3 phosphorylation by pathogenic LRRK2 impairs trafficking of synaptic vesicle precursors
By onGain-of-function mutations in LRRK2 gene lead to by increasing phosphorylation of RAB GTPases. Over-phosphorylation of RAB3A disrupts synaptic vesicle transport in human neurons, altering synaptic protein distribution and likely contributing to PD.
The GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in human cell lines
By onThe GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in fibroblasts.
Black and African American Connections to Parkinson’s Disease Study: Addressing Missing Diversity in Parkinson’s Disease Genetics
By onOur current understanding of Parkinson's disease and atypical parkinsonism-related syndromes is disproportionately based on studying populations of European ancestry, leading to a significant gap of knowledge concerning clinical features, genetics, and pathophysiology underlying disease etiology in underrepresented populations, including Black and African American individuals.
