Cognitive dysfunction in animal models of human lewy-body dementia
By onSynucleinopathies like Parkinson’s Disease Dementia are linked to cognitive impairments due to Lewy bodies. Various methods, like genetic manipulation and toxin exposure, can model these pathologies in research to understand human diseases better.
Insights into VPS13 properties and function reveal a new mechanism of eukaryotic lipid transport
By onRecent studies of VPS13 protein family reveal a novel intracellular lipid transport mechanism involving rod-like proteins forming a bridge with a hydrophobic groove for lipid transport, where their dysfunction may lead to disease.
Endoplasmic Reticulum Membrane Contact Sites, Lipid Transport, and Neurodegeneration
By onThe Endoplasmic Reticulum (ER) is crucial for cell function, interacting with other organelles through membrane contact sites. Mutations affecting ER proteins can lead to neurodegenerative diseases by disrupting lipid transport in cells.
Characterizing enteric neurons in dopamine transporter (DAT)-Cre reporter mice reveals dopaminergic subtypes with dual-transmitter content
By onUsing a reporter mouse line expressing tdTomato under control of DAT promoter in the gut and single cell sequencing we uncovered a novel population of DA neurons unique to the ENS which was ChAT/DAT-tdTomato-immunoreactive and expressed Grp, Calcb.
Reconstitution of BNIP3/NIX-mediated autophagy reveals two pathways and hierarchical flexibility of the initiation machinery
By onDuring selective autophagy transmembrane cargo receptors can trigger autophagy by recruiting different complexes and utilizing multiple pathways. This flexibility in autophagy initiation has important therapeutic implications.
Movement-related activity in the internal globus pallidus of the parkinsonian macaque
By onThis study of MPTP-induced parkinsonism in macaques indicates that changes in the timing of task-related neural activity of the internal segment of the globus pallidus (GPi) correlate with the severity of motor impairments.
Induced Pluripotent Stem Cells: A Tool for Modelling Parkinson’s Disease
By onPD involves loss of dopaminergic neurons in the substantia nigra. Patient-derived iPSC models aid in understanding the disease and identifying potential treatments. More research is needed on age-related aspects and gene-environment interactions.
Prospects for Disease Slowing in Parkinson Disease
By onDespite advancements in understanding PD pathogenesis and developing targeted therapies, no treatment has proven effective in modifying the disease. This review discusses current pharmacological interventions in clinical trials for PD.
Segregated basal ganglia output pathways correspond to genetically divergent neuronal subclasses
By onOur findings in this paper provide a unifying logic for how the developmental specification of diverse SNr neurons relates to the anatomical organization of basal ganglia circuits controlling specialized downstream brain regions.
Interactions of dopamine, iron, and alpha-synuclein linked to dopaminergic neuron vulnerability in Parkinson’s disease and Neurodegeneration with Brain Iron Accumulation disorders
By onDopamine, alpha-syn, and iron dysregulation contribute to vulnerability of substantia nigra dopaminergic neurons in Parkinson's and related disorders. Understanding their interplay is crucial for developing treatments to prevent disease progression.
Gut microbiome-mediated regulation of neuroinflammation
By onGut microbiome influences neuroinflammatory disease through pathways, including metabolite production, immune cell trafficking, and vagus nerve. Research on gut-brain axis has promising implications for understanding and treating neuroinflammation.
Similarities and differences between nigral and enteric dopaminergic neurons unravel distinctive involvement in Parkinson’s disease
By onParkinson's disease affects both midbrain and enteric nervous system dopaminergic neurons. Shared factors and properties control their evolution, with potential for novel neurotrophic factors to be used as protection against PD symptoms in the ENS.
Endo-IP and Lyso-IP Toolkit for Endolysosomal Profiling of Human-Induced Neurons
By onThe endolysosomal system regulates plasma membrane protein homeostasis and is crucial for neuronal function and implicated in Parkinson's disease. We present a proteomics tool to analyze the endolysosomal system in human induced cortical-like neurons
Abnormal hyperactivity of specific striatal ensembles encodes distinct dyskinetic behaviors revealed by high-resolution clustering
By onL-DOPA-induced dyskinesia is a common issue in Parkinson's disease due to dopamine therapy. These findings show that ensembles of behavior-encoding D1- and D2-SPNs form new combinations of hyperactive neurons mediating specific dyskinetic movements.
Baseline α-synuclein seeding activity and disease progression in sporadic and genetic Parkinson’s disease in the PPMI cohort
By onStudy analyzed α-synuclein seeding activity in Parkinson's patients from PPMI cohort. No significant association found between baseline α-syn seeding activity and disease progression in sporadic PD, LRRK2 PD, and GBA PD.
DIO-SPOTlight Transgenic Mouse to Functionally Monitor Protein Synthesis Regulated by the Integrated Stress Response
By onA new SPOTlight reporter allows visualization of the integrated stress response (ISR) activity in specific cell types in transgenic mice, aiding in studying health and disease implications.
Spatial genomics of AAVs reveals mechanism of transcriptional crosstalk that enables targeted delivery of large genetic cargo
By onThe authors identify widespread transcriptional crosstalk between enhancers and promoters delivered in different AAV vectors. They show that this arises from concatemerization and harness it to deliver large cargo for cell type-specific gene editing.
Structural analyses define the molecular basis of clusterin chaperone function
By onStructure-based functional analysis of the medically important extracellular chaperone and apolipoprotein Clusterin, revealed two hydrophobic tails key for chaperone function, membrane receptor binding, cellular uptake, and apolipoprotein formation.
Viral overexpression of human alpha-synuclein in mouse substantia nigra dopamine neurons results in hyperdopaminergia but no neurodegeneration
By onNovel viral vector for α-syn overexpression, AAV-DIO-hASYNWT, can be expressed selectively in neuronal populations based on Cre. Overexpression in DANs did not cause degeneration. AAV-DIO-hASYNWT increased DA levels and locomotor hyperactivity.
Progressive noradrenergic degeneration and motor cortical dysfunction in Parkinson’s disease
By onThe article discusses clinical and preclinical studies that support the critical rolLC-NE neurodegeneration and motor cortical dysfunction in both motor and nonmotor deficits in Parkinsonian states.
