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.
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.
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.
Subsecond Analysis of Locomotor Activity in Parkinsonian Mice
By onThis work documents robust changes in the velocity, usage, and temporal organization of behavioral modules, as well as their responsiveness to dopaminergic treatment under the Parkinsonian state.
⍺-Synuclein levels in Parkinson’s disease – Cell types and forms that contribute to pathogenesis
By onParkinson's disease is characterized by dopamine neuron loss and ⍺-synuclein aggregations in neurons. Research focuses on understanding the levels, modifications, and impact of ⍺-synuclein in brain cells, including non-neuronal cells.
Consensus Guidance for Genetic Counseling in GBA1 Variants: A Focus on Parkinson’s Disease
By onThis review discusses the link between *GBA1* and PD, testing practicalities, and counseling approaches.
Targeting mitophagy in neurodegenerative diseases
By onMitochondrial dysfunction is key in neurodegenerative diseases like Parkinson's and Alzheimer's. Enhancing mitophagy could be a new therapeutic approach, with USP30 inhibitors and PINK1 activators in phase I trials for potential disease modification.
Glycolipids in Parkinson’s disease: beyond neuronal function
By onGlycolipid balance is crucial for normal body function and its disruption can cause diseases like Parkinson's. Understanding glycolipid pathways can help develop treatments for neurodegenerative diseases like PD.
Mediterranean Diet Adherence, Gut Microbiota and Parkinson’s Disease: A Systematic Review
By onHigh adherence to the Mediterranean diet may improve cognitive function and gastrointestinal symptoms in Parkinson's disease patients, possibly due to changes in gut microbiota. More research is needed to understand its effects on motor symptoms.
The gut microbiome promotes mitochondrial respiration in the brain of a Parkinson’s disease mouse model
By onIn this paper, the authors find that the gut microbiome increases mitochondrial respiration and oxidative stress in the brain, which enhances motor symptoms in a mouse model of PD.
Lysosomal Glucocerebrosidase is needed for ciliary Hedgehog signaling: A convergent pathway to Parkinson’s disease
By onLoss of dopamine neurons in Parkinson's disease is linked to mutations in *LRRK2* and *GBA1*. Both mutations inhibit Hedgehog signaling, reducing production of neuroprotective factors. This reveals a common mechanism contributing to PD pathogenesis.
α-Synuclein aggregates inhibit ESCRT-III through sequestration and collateral degradation
By onα-Synuclein aggregates deplete ESCRT-III by sequestration and "collateral degradation," impeding endolysosomal repair. This allows endocytosed fibrils to leak into the cytoplasm, triggering a toxic cycle of aggregation and endolysosomal dysfunction.
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.
LINE-1 retrotransposons mediate cis-acting transcriptional control in human pluripotent stem cells and regulate early brain development
By onHominoid-specific L1 retrotransposons are expressed in human stem cells and organoids. Silencing L1s leads to changes in neural differentiation and organoid size, suggesting L1 involvement in central nervous system development.
