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.
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.
CHCHD2 mutant mice link mitochondrial deficits to PD pathophysiology
By onMutations in mitochondrial protein CHCHD2 lead to a form of Parkinson's disease. CHCHD2 T61I mutant mice show molecular changes in the brain, altered metabolism favoring glycolysis, and disrupted mitochondrial function in dopamine neurons.
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.
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.
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.
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.
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.
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.
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
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.
Cell-type resolved protein atlas of brain lysosomes identifies SLC45A1-associated disease as a lysosomal disorder
By onA study identified new lysosomal proteins in brain cells, including SLC45A1, linked to a neurological disease. Loss of SLC45A1 disrupts lysosomal function, impacting V-ATPase stability and causing mitochondrial dysfunction.
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.
Single cell long read whole genome sequencing reveals somatic transposon activity in human brain
By onSingle cell long-read sequencing uncovers novel dynamics in three brains, shedding light on genomic variability. It reveals brain-specific transposable element activity, offering crucial insights into individual cell genomes.
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.
State-dependent modulation of spiny projection neurons controls levodopa-induced dyskinesia in a mouse model of Parkinson’s disease
By onLID is poorly understood, our research on dyskinetic mice show SPNs' properties oscillate during LID and are influenced by dopamine and acetylcholine signaling. Targeting M1 receptors in iSPNs reduced LID severity and improved levodopa effects.
