PathMap Literature Based Discovery Engine

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Experiment #00000139

Foundational Dietary Theory: The dietary synergy between Hi-Maize and 6x Spermidine Yeast creates a potential cellular supply-and-clearance loop within the brain's astrocytes. Circulating spermidine metabolites utilize documented astrocytic polyamine uptake systems to access the central nervous system. Once inside, this exogenous spermidine drives FAM134B-mediated ER-phagy, clearing the endoplasmic reticulum matrix. This clearance removes the ER-stress bottleneck, allowing newly transcribed astrocytic EAAT2—upregulated by gut-derived butyrate from Hi-Maize fermentation—to successfully traffic to the plasma membrane and mitigate synaptic glutamate excitotoxicity.

Starch, Resistant _gates_from_starch__resistant Butyric Acid _gates_to_butyric_acid _gates_from_butyric_acid Glutamate Plasma Membrane Transport Proteins _gates_to_glutamate_plasma_membrane_transport_proteins Spermidine _gates_from_spermidine Autophagy
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Experiment #00000137

Organic solvent exposure as an environmental risk factor associated with multiple sclerosis pathogenesis.

Genetic susceptibility _gates_from_genetic_susceptibility Environmental exposures _gates_to_environmental_exposures _gates_from_environmental_exposures Solvents _gates_to_solvents _gates_from_solvents Incidence _gates_to_incidence
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Experiment #00000132

Discovery: Considering PubMed #41177462, intranasal S-GEVs co-functionalized with ApoE peptides may bypass the cribriform plate and target astrocytic LRP1 receptors in order to suppress NF-κB and may resolve some neuroinflammation in Alzheimer's and ALS.

Administration, Intranasal _gates_from_administration__intranasal Blood-Brain Barrier _gates_to_blood_brain_barrier Apolipoproteins E _gates_from_apolipoproteins_e Low Density Lipoprotein Receptor-Related Protein-1 _gates_to_low_density_lipoprotein_receptor_related_protein_1 Signal Transduction _gates_from_signal_transduction
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Experiment #00000131

Premise: Environmental metals, though present in many Amyotrophic Lateral Sclerosis anomalous clusters, are debated regarding causality within geographic epistemological data. Hypothesis: If plant derived extracellular vesicles (PDEVs) aerosolized with environmental metals, they could potentially bypass the blood brain barrier via the cribriform plate area. Given this potential method of delivery, environmental metals cannot be ruled out as causal in sporadic ALS until PDEV delivery of the metals is tested in wet lab experiments, but may potentially explain the confounding data.

Environmental Pollutants _gates_from_environmental_pollutants PDEV association _gates_to_pdev_association _gates_from_pdev_association Nose-to-Brain Delivery _gates_to_nose_to_brain_delivery _gates_from_nose_to_brain_delivery Brain Diseases _gates_to_brain_diseases
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Experiment #00000130

Targeted alteration of the oral microbiome via a single polyphenol- and fiber-dense meal plan creates an immediate shift in the microbial composition of involuntary nocturnal microaspiration droplets. Upon entry into the lower respiratory tract, this eubiotic bacterial influx acts as an acute molecular signal that rapidly modulates microglia reactivity and neuroinflammation via the lung-brain axis, bypassing systemic colonic metabolite transport.

Dietary modification _gates_from_dietary_modification Dysbiosis _gates_to_dysbiosis _gates_from_dysbiosis Respiratory Aspiration _gates_to_respiratory_aspiration _gates_from_respiratory_aspiration Microglia _gates_to_microglia
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Experiment #00000127

Neuroinflammatory astrocyte subtypes in the mouse brain

Pathologic Processes _gates_from_pathologic_processes Gene Expression Regulation _gates_to_gene_expression_regulation _gates_from_gene_expression_regulation Biological Phenomena _gates_to_biological_phenomena _gates_from_biological_phenomena Neuroinflammatory Diseases _gates_to_neuroinflammatory_diseases
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Experiment #00000126

Hypothesis: Intranasal delivery of Spermidine-modified Ginseng Extracellular Vesicles (S-GEVs) loaded with multi-targeted mRNA suppresses MARK2-eIF2α-driven RAN translation to prevent dipeptide repeat clogging of FG-nucleoporins, synergizing with progranulin-mediated lysosomal clearance to arrest TMEM106B amyloid accumulation and block the execution of p38-Lamin B1-dependent Karyoptosis in motor neurons.

Spermidine _gates_from_spermidine Lysosomal Degradation _gates_to_lysosomal_degradation _gates_from_lysosomal_degradation Protein Aggregates _gates_to_protein_aggregates _gates_from_protein_aggregates Cell Death _gates_to_cell_death
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Experiment #00000124

Hypothesis: Intranasal delivery of Spermidine-modified Ginseng Extracellular Vesicles (S-GEVs) loaded with GRN mRNA exploits the cribriform plate anatomy to bypass the blood-brain barrier, providing a neuro-targeted delivery system for progranulin gene therapy that acts synergistically with spermidine-induced autophagy to suppress pathological TMEM106B amyloid accumulation and restore endolysosomal homeostasis.

Administration, Intranasal _gates_from_administration__intranasal Olfactory Bulb _gates_to_olfactory_bulb Progranulins _gates_from_progranulins _gates_to_progranulins RNA, Messenger _gates_from_rna__messenger PGRN protein
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Experiment #00000123

Hypothesis: Intranasal delivery of Spermidine-modified Ginseng Extracellular Vesicles (S-GEVs) loaded with GRN mRNA exploits the cribriform plate anatomy to bypass the blood-brain barrier, providing a neuro-targeted delivery system for progranulin gene therapy that acts synergistically with spermidine-induced autophagy to suppress pathological TMEM106B amyloid accumulation and restore endolysosomal homeostasis.

Administration, Intranasal _gates_from_administration__intranasal Olfactory Bulb _gates_to_olfactory_bulb Progranulins _gates_from_progranulins _gates_to_progranulins RNA, Messenger _gates_from_rna__messenger PGRN protein
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Experiment #00000119

Hypothesis: Considering PubMed #41177462, Intranasally administered GDEVs, specifically spermidine-modified ginger extracellular vesicles, may offer a multi-target therapeutic strategy for C9orf72-associated ALS by crossing the blood-brain barrier via olfactory routes to potentially deliver gene-editing components, support axonal translation, restore STMN2 expression, and attenuate neuroinflammation.

Spermidine _gates_from_spermidine Olfactory Bulb _gates_to_olfactory_bulb Drug Delivery Systems _gates_from_drug_delivery_systems Stathmin 2 _gates_to_stathmin_2 Eukaryotic Initiation Factor-5A _gates_from_eukaryotic_initiation_factor_5a
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Experiment #00000118

Environmental plant-derived extracellular vesicles (such as those from pollen or agricultural dust) may act as stealth vectors via nasal-olfactory pathways, potentially delivering environmental toxins or pathogenic RNAs that bypass the BBB and trigger neurodegenerative pathologies, such as Amyotrophic Lateral Sclerosis.

Olfactory Pathways _gates_from_olfactory_pathways Extracellular Vesicles _gates_to_extracellular_vesicles _gates_from_extracellular_vesicles Biological Factors _gates_to_biological_factors _gates_from_biological_factors Amyotrophic Lateral Sclerosis _gates_to_amyotrophic_lateral_sclerosis
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Experiment #00000117

Ginger Derived Extracellular Vesicles may be a therapeutic hack for nasal C9orf72 CRISPR delivery, bypassing the BBB via nerve pathways to widely distribute gene edits without toxicity.

Drug Delivery Systems _gates_from_drug_delivery_systems _gates_to_drug_delivery_systems CRISPR-Cas Systems _gates_to_crispr_cas_systems Nanoparticles _gates_from_nanoparticles Blood-Brain Barrier _gates_to_blood_brain_barrier Intranasal Administration
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Experiment #00000116

How do electrophilic binding and charge polarity modulate proteinopathy in Alzheimer's Disease, specifically regarding BBB interactions?

Metabolic State _gates_from_metabolic_state βHB Production _gates_to___hb_production 3-Hydroxybutyric Acid _gates_from_3_hydroxybutyric_acid Protein Aggregates _gates_to_protein_aggregates _gates_from_protein_aggregates Autophagy
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Experiment #00000112

Exploration of fermentation of plant roots used as a gut-brain axis mediator to reduce microglia activation and inflammation.

Plant Roots _gates_from_plant_roots Fermentation _gates_to_fermentation _gates_from_fermentation Gut-Brain Axis _gates_to_gut_brain_axis _gates_from_gut_brain_axis Microglia _gates_to_microglia
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Experiment #00000101

Hypothesis: If Botox were injected into the nerve ending on the third toe on the left foot, the toxin can "climb" retrograde from toe through motor neurons eventually to the brain and temporarily inhibit vesicular docking "from toe to head", potentially allowing a timed pharmacological therapeutic window for toxic EV clearance through the lymph system instead of docking and seeding.

Botulinum Toxins, Type A _gates_from_botulinum_toxins__type_a Axonal Transport _gates_to_axonal_transport _gates_from_axonal_transport SNARE Proteins _gates_to_snare_proteins _gates_from_snare_proteins Lymphatic Vessel Endothelial Hyaluronan Receptor-1 _gates_to_lymphatic_vessel_endothelial_hyaluronan_receptor_1
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Experiment #00000094

Hypothesis: If studied by scientists, pickled ginseng may be found to have therapeutic use in treating gut dysbiosis, potentially acting as a pathway to reduce neuroinflammation in some neurodegenerative diseases such as ALS.

Ginseng _gates_from_ginseng Gut Microbiota _gates_to_gut_microbiota _gates_from_gut_microbiota Neuroinflammation _gates_to_neuroinflammation _gates_from_neuroinflammation Neurodegenerative Diseases _gates_to_neurodegenerative_diseases
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Experiment #00000093

What is the core mechanism that Almased uses to improve metabolism and liver function and can the mechanism be repurposed as a therapeutic in neurodegenerative disease via the gut-brain axis?

Dietary Therapy _gates_from_dietary_therapy Intestinal Mucosa _gates_to_intestinal_mucosa _gates_from_intestinal_mucosa Inflammation Mediators _gates_to_inflammation_mediators Pro-inflammatory mediators _gates_from_pro_inflammatory_mediators Gastrointestinal Microbiome
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Experiment #00000092

A Top-Down Mechanism for Sporadic ALS Initiated by Ocular Metal Dyshomeostasis and Retrograde Exosomal Transport along the Subcortical Visual Axis

Eye Diseases _gates_from_eye_diseases Retinal Diseases _gates_to_retinal_diseases _gates_from_retinal_diseases Extracellular Vesicles _gates_to_extracellular_vesicles _gates_from_extracellular_vesicles Motor Neurons _gates_to_motor_neurons
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Experiment #00000086

Parkinson's Disease versus Alzheimer's Disease: Shared and Exclusive Pathways

Pathologic Processes _gates_from_pathologic_processes Mitochondrial Diseases _gates_to_mitochondrial_diseases Lipid Metabolism Disorders _gates_from_lipid_metabolism_disorders Lipid Droplet Accumulation _gates_to_lipid_droplet_accumulation _gates_from_lipid_droplet_accumulation Lysosomal Storage Diseases
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Experiment #00000083

Dietary strategy: High amylose maize starch may be identified as a non-invasive tool to improve outcomes in TBI, and potentially hypoxic neurovascular damage, suggesting it could be repurposed for high-altitude workers or elderly patients with cognitive frailty.

High Amylose Maize Starch (HAMS) _gates_from_high_amylose_maize_starch__hams_ Fatty Acids, Volatile _gates_to_fatty_acids__volatile _gates_from_fatty_acids__volatile Blood-Brain Barrier _gates_to_blood_brain_barrier _gates_from_blood_brain_barrier Brain Injuries, Traumatic _gates_to_brain_injuries__traumatic
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Experiment #00000082

Microbiota-derived acetate can alleviate neurological inflammation and neurodegeneration induced by hypoxia via the upregulation of brain-derived neurotrophic factor (BDNF).

Hypoxia _gates_from_hypoxia Dysbiosis _gates_to_dysbiosis _gates_from_dysbiosis Acetic Acid _gates_to_acetic_acid _gates_from_acetic_acid Neuroinflammation _gates_to_neuroinflammation
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Experiment #00000075

Polystyrene nanoplastics (PS-NPs) may act as a scaffold for the recruitment and accumulation of WDR44 at the lysosomal membrane, thereby accelerating the de novo aggregation of alpha-synuclein in the early stages of PD.

Nanoplastic exposure _gates_from_nanoplastic_exposure Lysosomal Storage Diseases _gates_to_lysosomal_storage_diseases _gates_from_lysosomal_storage_diseases alpha-Synuclein _gates_to_alpha_synuclein WDR44 _gates_from_wdr44 Protein Aggregates
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Experiment #00000074

OGT (O-GlcNAc transferase) modulation via pharmacological agonists can prevent degeneration of cranial nerves following traumatic or surgical stress.

Trauma/Stress _gates_from_trauma_stress Ferritinophagy/Oxidative Stress _gates_to_ferritinophagy_oxidative_stress Autophagy _gates_from_autophagy N-Acetylglucosaminyltransferases _gates_to_n_acetylglucosaminyltransferases _gates_from_n_acetylglucosaminyltransferases Neuronal Survival
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Experiment #00000073

Can botulinum toxin A (BTX-A) be repurposed from cosmetic/spasticity applications in order to treat oculomotor palsy and have utilization with endoscopic endonasal approaches to skull base tumors to protect cranial nerves?

Botulinum Toxins, Type A _gates_from_botulinum_toxins__type_a Muscle Relaxation _gates_to_muscle_relaxation _gates_from_muscle_relaxation Neuroprotection _gates_to_neuroprotection Oculomotor Nerve Diseases _gates_from_oculomotor_nerve_diseases BTX-A
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Experiment #00000071

Do any recent non-proliferative diabetic retinopathy clinical trials reveal anything about Amyotrophic Lateral Sclerosis?

Diabetic Retinopathy _gates_from_diabetic_retinopathy ALS _gates_to_als Retinal Diseases _gates_to_retinal_diseases _gates_from_retinal_diseases Neurodegenerative Diseases _gates_to_neurodegenerative_diseases _gates_from_neurodegenerative_diseases
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Experiment #00000070

What types of infections might cause a high C-Reactive Protein result?

Pathogen presence _gates_from_pathogen_presence Immunity, Innate _gates_to_immunity__innate _gates_from_immunity__innate C-Reactive Protein _gates_to_c_reactive_protein _gates_from_c_reactive_protein Biomarkers _gates_to_biomarkers
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Experiment #00000066

Are there any wellness alternatives for Von Willebrand Disease?

von Willebrand Diseases _gates_from_von_willebrand_diseases Multidisciplinary Care _gates_to_multidisciplinary_care _gates_from_multidisciplinary_care Transcutaneous Electric Nerve Stimulation _gates_to_transcutaneous_electric_nerve_stimulation Electric Stimulation Therapy _gates_to_electric_stimulation_therapy _gates_from_electric_stimulation_therapy
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Experiment #00000065

Does pathologically seeded TDP-43 exit the retina via anterograde axonal transport along the optic tract to midbrain hubs, enter the systemic circulation inside extracellular vesicles, and subsequently traffic into pancreatic beta-cells to accelerate type 2 diabetes phenotypes?

TAR DNA-Binding Protein 43 _gates_from_tar_dna_binding_protein_43 Extracellular Vesicles _gates_to_extracellular_vesicles Systemic circulating EVs _gates_from_systemic_circulating_evs Insulin-Secreting Cells _gates_to_insulin_secreting_cells Axonal Transport _gates_to_axonal_transport
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Experiment #00000064

Lon Protease, Alternaria; IL-33; TSLP; alarmins; asthma; chronic rhinosinusitis; fungal allergen; innate lymphoid cells

Alternaria _gates_from_alternaria Alarmins _gates_to_alarmins _gates_from_alarmins Immunity, Innate _gates_to_immunity__innate _gates_from_immunity__innate Lon-Peptidase _gates_to_lon_peptidase
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Experiment #00000056

Sarcopenia and Amyotrophic Lateral Sclerosis: Biological Pathways and Analysis

Motor Neuron Disease _gates_from_motor_neuron_disease Neuromuscular Junction Diseases _gates_to_neuromuscular_junction_diseases _gates_from_neuromuscular_junction_diseases Muscle Weakness _gates_to_muscle_weakness NMJ instability _gates_from_nmj_instability Sarcopenia
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Experiment #00000054

What dietary habits are beneficial towards reducing excess/harmful tyramine in order to improve liver and gut health?

Dietary Proteins _gates_from_dietary_proteins Aromatic-L-Amino-Acid Decarboxylases _gates_to_aromatic_l_amino_acid_decarboxylases _gates_from_aromatic_l_amino_acid_decarboxylases Tyramine _gates_to_tyramine _gates_from_tyramine Gastrointestinal Diseases _gates_to_gastrointestinal_diseases
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Experiment #00000047

Does blast-induced mild traumatic brain injury (mTBI) drive progressive tau/TDP-43 seeding by disrupting astrocytic AQP4 glymphatic clearance and activating microglial cGAS-STING neuroinflammation? #mTBI #Glymphatic #cGASSTING

Blast Injuries _gates_from_blast_injuries Aquaporin 4 _gates_to_aquaporin_4 _gates_from_aquaporin_4 Glymphatic System _gates_to_glymphatic_system _gates_from_glymphatic_system Protein Aggregates _gates_to_protein_aggregates
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Experiment #00000038

Map the direct mechanical and axonal transport pathways connecting intranasal administration or trigeminal nerve delivery to the clearance of TDP-43 aggregates in sporadic ALS, and the delivery of CRISPR-Cas/ASO gene therapies targeting C9orf72 hexanucleotide repeat expansions in the cerebellum and brainstem.

Intranasal Route _gates_from_intranasal_route Blood-Brain Barrier _gates_to_blood_brain_barrier C9orf72 Protein _gates_to_c9orf72_protein _gates_from_c9orf72_protein Brain _gates_to_brain Intranasal Administration
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Experiment #00000031

Why are frontotemporal dementia and c9orf72 ALS considered different diseases if they are both driven by the same abnormal expansion of a GGGGCC (G₄C₂) sequence in the first intron of the C9orf72 gene? Is it logical to think that CRISPR therapeutics for FTD potentially be used for ALS as well?

C9orf72 expansion _gates_from_c9orf72_expansion Gene Expression Regulation _gates_to_gene_expression_regulation _gates_from_gene_expression_regulation Protein Aggregation, Pathological _gates_to_protein_aggregation__pathological _gates_from_protein_aggregation__pathological CRISPR-Cas Systems _gates_to_crispr_cas_systems
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Experiment #00000030

Can AI and single-cell RNA sequencing help map cryptic TDP-43 splicing errors in sporadic ALS to design BBB-penetrant CRISPR gene therapies before neurotoxicity begins?

Single-Cell Analysis _gates_from_single_cell_analysis RNA Splicing _gates_to_rna_splicing _gates_from_rna_splicing Blood-Brain Barrier _gates_to_blood_brain_barrier _gates_from_blood_brain_barrier Neurotoxicity Syndromes _gates_to_neurotoxicity_syndromes
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Experiment #00000029

Why do people get tinnitus and are there any wellness alternatives to help reduce the impact it has on lifestyle and comfort?

Cochlear Diseases _gates_from_cochlear_diseases Neuronal Plasticity _gates_to_neuronal_plasticity _gates_from_neuronal_plasticity Tinnitus _gates_to_tinnitus _gates_from_tinnitus Health Promotion _gates_to_health_promotion
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Experiment #00000027

How does eating legumes and vegetables help restore gut-brain axis homeostasis?

Vegetables _gates_from_vegetables Gastrointestinal Microbiome _gates_to_gastrointestinal_microbiome _gates_from_gastrointestinal_microbiome Inflammation _gates_to_inflammation _gates_from_inflammation Neuroprotection _gates_to_neuroprotection
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Experiment #00000025

How does sarcopenia feel versus Amyotrophic Lateral Sclerosis fasciculations or age-related proximal myopathy?

Sarcopenia _gates_from_sarcopenia Clinical Symptomatology _gates_to_clinical_symptomatology Muscular Atrophy _gates_to_muscular_atrophy ALS _gates_from_als Neuromuscular Diseases _gates_to_neuromuscular_diseases
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Experiment #00000018

Can smoking cigarettes cause dysbiosis?

Tobacco Smoke Pollution _gates_from_tobacco_smoke_pollution Epithelium _gates_to_epithelium _gates_from_epithelium Dysbiosis _gates_to_dysbiosis _gates_from_dysbiosis Immune System Diseases _gates_to_immune_system_diseases
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Experiment #00000017

How does the gut-brain axis play a role in Alzheimer's Disease? Is there a potential link for gut-brain axis for other neurological disorders such as Amyotrophic Lateral Sclerosis?

Dysbiosis _gates_from_dysbiosis Intestinal Permeability _gates_to_intestinal_permeability _gates_from_intestinal_permeability Systemic Inflammatory Response Syndrome _gates_to_systemic_inflammatory_response_syndrome _gates_from_systemic_inflammatory_response_syndrome Neuroinflammation _gates_to_neuroinflammation
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Experiment #00000014

Under certain conditions, can hyperexcited retinal ganglion cells misfire corollary discharge(s) unexpectedly?

Oculomotor Motor Command _gates_from_oculomotor_motor_command Corollary Discharge _gates_to_corollary_discharge _gates_from_corollary_discharge Sensory Processing, Sensory _gates_to_sensory_processing__sensory Retinal Ganglion Cells (RGCs) _gates_from_retinal_ganglion_cells__rgcs_ Visual Perception
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Experiment #00000012

If a toxin with a thermodynamic affinity for Zinc GREATER THAN that of Glutamate AND LESS THAN that of RGNEF, under certain conditions a pathway exists wherein the toxin could shuttle synaptic retinal zinc to RGNEF, thus potentially ultimately resulting in the retinal TDP-43 proteinopathy seen in the retina post mortem in Sporadic Amyotrophic Lateral Sclerosis

Synaptic Zinc _gates_from_synaptic_zinc Receptors, Glutamate _gates_to_receptors__glutamate _gates_from_receptors__glutamate Zinc Dyshomeostasis in RGCs _gates_to_zinc_dyshomeostasis_in_rgcs _gates_from_zinc_dyshomeostasis_in_rgcs TDP-43 Proteinopathy _gates_to_tdp_43_proteinopathy
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Experiment #00000004

Can the identified lysosomal-targeted acidic nanoparticles (AcNPs) or specific small-molecule chaperones effectively reverse established alpha-synuclein aggregation in chronic exposure models, and do they provide neuroprotection against subsequent environmental pollutant insults?

Lysosomal Storage Diseases _gates_from_lysosomal_storage_diseases alpha-Synuclein _gates_to_alpha_synuclein Alpha-synuclein aggregation _gates_from_alpha_synuclein_aggregation Molecular Chaperones _gates_to_molecular_chaperones Lysosomes _gates_from_lysosomes
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Experiment #00000003

Does long-term microplastic or bisphenol exposure act as a catalyst for alpha-synucleitin aggregation in Parkinson's disease by disrupting lysosomal membrane permeabilization?

Environmental Exposure _gates_from_environmental_exposure Endolysosomes _gates_to_endolysosomes _gates_from_endolysosomes Lysosomal Membranes _gates_to_lysosomal_membranes _gates_from_lysosomal_membranes Autophagy _gates_to_autophagy
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Experiment #00000002

Does chronic latent Epstein-Barr Virus (EBV) reactivation drive microglial activation and subsequent myelin destruction in Multiple Sclerosis via the activation of the cGAS-STING innate immune pathway?

Epstein-Barr Virus Infections _gates_from_epstein_barr_virus_infections Microglial Activation _gates_to_microglial_activation _gates_from_microglial_activation cGAS-STING Signaling _gates_to_cgas_sting_signaling _gates_from_cgas_sting_signaling Demyelinating Diseases _gates_to_demyelinating_diseases
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