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.
⍺-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.
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.
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.
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.
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.
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.
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.
Exploring the relationship between GBA1 host genotype and gut microbiome in the GBA1L444P/WT mouse model: Implications for Parkinson disease pathogenesis
By onHeterozygous *GBA1* variants are common in Parkinson's disease. This study found no significant impact of the *GBA1* L444P variant on gut microbiome composition in mice, suggesting other factors may contribute to disease penetrance.
Severe GBA1 variants drive the GBA-PD clinical phenotype: implications for counselling and clinical trials
By onVariants in the GBA1 gene are common genetic risk factors for Parkinson's disease. A study compared clinical phenotypes in GBA-PD and idiopathic PD patients, finding that only severe GBA-PD cases show a more severe clinical profile.
Postsynaptic adaptations in direct pathway muscarinic M4-receptor signaling follow the temporal and regional pattern of dopaminergic degeneration
By onImbalances in dorsal striatum output in Parkinson's disease are driven by dopamine loss and disrupted acetylcholine signaling. These changes occur in response to dopamine loss, affecting M4 receptors in striatal neurons, crucial for PD progression.
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.
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.
EndoMAP.v1, a Structural Protein Complex Landscape of Human Endosomes
By onEarly endosomes regulate protein fate, sorting plasma membrane proteins for recycling or degradation. Cross-linking and computational analysis were used to create a human endosomal structural interactome, revealing potential regulatory mechanisms.
PPM1M, a LRRK2-counteracting, phosphoRab12-preferring phosphatase with potential link to Parkinson’s disease
By onLRRK2 phosphorylates Rab GTPases linked to Parkinson's disease. PPM1M identified as a phosphatase reversing Rab phosphorylation, crucial in LRRK2 pathway. PPM1M mutation found in Parkinson's patients, suggesting a new therapeutic target.
In situ cryo-ET visualization of mitochondrial depolarization and mitophagic engulfment
By onApplication of in situ cryo-electron tomography (cryo-ET) to visualize the consequences of mitochondrial depolarization at higher resolution.
