PathMap Literature Based Discovery Engine

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Experiment #00000138

Dietary butyrate from resistant starch may synergize with sulforaphane-driven Nrf2 activation and spermidine-mediated FAM134B ER-phagy in order to restore astrocytic EAAT2 membrane trafficking and potentially clear synaptic glutamate excitotoxicity in neurodegeneration. (Literature Based Discovery)

Starch, Resistant _gates_from_starch__resistant Butyrate _gates_to_butyrate _gates_from_butyrate NF-E2-Related Factor 2 _gates_to_nf_e2_related_factor_2 Sulforaphane _gates_from_sulforaphane Spermidine
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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 #00000133

ApoE-mediated lipsignaling and EV-delivered bioenergetic substrates both converge on the stabilization of mitochondrial respiratory complexes, which is the requisite physiological precursor for renewed neurogenesis in the hippocampus.

Apolipoprotein E4 _gates_from_apolipoprotein_e4 Mitochondrial Respiration _gates_to_mitochondrial_respiration Extracellular Vesicles _gates_from_extracellular_vesicles Mitochondria _gates_to_mitochondria Energy Metabolism _gates_from_energy_metabolism
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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 #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 #00000114

Biohack, Anti-Ebola Hypothesis 1: PDEV-to-macrophage siRNA targeting VP40 Load the plant vesicles with synthetic siRNAs designed to silence VP40 transcription directly inside the macrophage. Exploration of dietary, pharmacological, and repurposed solutions to achieve this.

PDEV isolation _gates_from_pdev_isolation RNA, Small Interfering _gates_to_rna__small_interfering _gates_from_rna__small_interfering Macrophage Activation _gates_to_macrophage_activation _gates_from_macrophage_activation Gene Silencing _gates_to_gene_silencing
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Experiment #00000111

Identify specific patterns of TDP-43 proteinopathy induced cryptic mis-splicing of STMN2 and other "cryptic mis-splicing" patterns found within PubMed Literature, 2026.

DNA-Binding Protein 43 _gates_from_dna_binding_protein_43 Exons _gates_to_exons _gates_from_exons Protein Deficiency _gates_to_protein_deficiency Functional Protein Loss _gates_from_functional_protein_loss Neurodegeneration
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Experiment #00000110

Karyoptosis mediates cell death and neurodegeneration upon proteotoxic stress.

Proteotoxic Stress _gates_from_proteotoxic_stress Cell Death _gates_to_cell_death _gates_from_cell_death Neurodegeneration _gates_to_neurodegeneration p38 Mitogen-Activated Protein Kinases _gates_to_p38_mitogen_activated_protein_kinases _gates_from_p38_mitogen_activated_protein_kinases
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Experiment #00000104

Candida Auris: Biological and Molecular Pathways, Phenotype Data

Segmental Duplications _gates_from_segmental_duplications Drug Resistance, Fungal _gates_to_drug_resistance__fungal Adaptation, Biological _gates_from_adaptation__biological Immune Evasion _gates_to_immune_evasion _gates_from_immune_evasion Metabolic Networks and Pathways
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Experiment #00000098

A 3x3 Evaluation Matrix of Biological Interactions of ARHGAP32, RGNEF (ARHGEF28), and TDP-43 in Neurodegenerative Disease found in PubMed Literature as of August 5, 2026

TDP-43 Proteinopathies _gates_from_tdp_43_proteinopathies RNA Splicing _gates_to_rna_splicing RGNEF (ARHGEF28) _gates_from_rgnef__arhgef28_ TDP-43 _gates_to_tdp_43
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Experiment #00000097

Evaluation of Known Roles of ARHGAP32, RGNEF (ARHGEF28), and TDP-43 in Neurodegenerative Disease found in PubMed Literature as of August 5, 2026

DNA-Binding Proteins _gates_from_dna_binding_proteins RNA Splicing _gates_to_rna_splicing _gates_from_rna_splicing Neuronal Plasticity _gates_to_neuronal_plasticity Synaptic Transmission _gates_to_synaptic_transmission Neuronal Dysfunction
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Experiment #00000096

analysis of the splicing landscape of the frontal cortex in ftld-tdp reveals subtype specific patterns and cryptic splicing

Frontotemporal Lobar Degeneration _gates_from_frontotemporal_lobar_degeneration Alternative Splicing _gates_to_alternative_splicing _gates_from_alternative_splicing RNA Splicing _gates_to_rna_splicing _gates_from_rna_splicing Subtype Specificity _gates_to_subtype_specificity
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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 #00000084

SOD1 Research July 2026

Genetic Testing _gates_from_genetic_testing Drug Delivery Systems _gates_to_drug_delivery_systems _gates_from_drug_delivery_systems Superoxide Dismutase-1 _gates_to_superoxide_dismutase_1 Protein Aggregates _gates_from_protein_aggregates Oxidative Stress
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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 #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 #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 #00000069

Keyword Analysis: diabetes; retinal diabetic neuropathy; ganglion cells; synapses; SPG302; tazbentetol; visual function; synaptic regeneration; neuroprotection; blindness; glaucoma

Glucose _gates_from_glucose Mitochondria _gates_to_mitochondria Mitochondrial Dysfunction _gates_from_mitochondrial_dysfunction Retinal Ganglion Cells _gates_to_retinal_ganglion_cells SPG302 Treatment _gates_from_spg302_treatment
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Experiment #00000067

Frontotemporal dementia; Splicing; TDP-43; Transcriptomics.

DNA-Binding Protein-43 _gates_from_dna_binding_protein_43 RNA Splicing _gates_to_rna_splicing _gates_from_rna_splicing Neuronal dysfunction _gates_to_neuronal_dysfunction Exons _gates_to_exons Splicing defects
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Experiment #00000063

What specific structural modifications to the pyrrolidinone scaffold led to improved potency against SARM1 compared to earlier inhibitor classes?

Pyrrolidinones _gates_from_pyrrolidinones SARM1 _gates_to_sarm1 Sterile Alpha and TIR Motif Containing 1 _gates_from_sterile_alpha_and_tir_motif_containing_1 Axonal Degeneration _gates_to_axonal_degeneration Molecular Structure _gates_from_molecular_structure
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Experiment #00000057

Amyotrophic Lateral Sclerosis breakthrough updates as of July 2026

Systemic Disease _gates_from_systemic_disease Gene Expression Regulation _gates_to_gene_expression_regulation
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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 #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 #00000045

Sporadic ALS and C9orf72 affected ALS are two different pathologies and the mixing of test groups and datasets has produced confounding results.

Molecular Heterogeneity _gates_from_molecular_heterogeneity Diagnostic Errors _gates_to_diagnostic_errors Biomarkers _gates_to_biomarkers Genetic Heterogeneity _gates_from_genetic_heterogeneity Molecular Typing _gates_to_molecular_typing
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Experiment #00000044

What kinds of changes in voice occur prior to Amyotrophic Lateral Sclerosis onset?

Amyotrophic Lateral Sclerosis _gates_from_amyotrophic_lateral_sclerosis Bulbar Palsy _gates_to_bulbar_palsy _gates_from_bulbar_palsy Speech _gates_to_speech _gates_from_speech Missing _gates_to_missing
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Experiment #00000039

What is the current evidence for RGNEF (ARHGEF28) functioning as a primary upstream regulator of axonal transport and TDP-43 homeostasis in ALS, and how does the failure of this 'terminal tether' initiate the pathological continuum compared to downstream protein aggregation?

Metabolic Stress _gates_from_metabolic_stress Protein Aggregation _gates_to_protein_aggregation _gates_from_protein_aggregation RNA Metabolism _gates_to_rna_metabolism _gates_from_rna_metabolism Axonal Transport _gates_to_axonal_transport
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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 #00000036

What is Karyoptosis and how does it align with past and present neurodegenerative disease research? Does Karyoptosis provide a new context in which a new class of repurposed therapeutics is formed?

Proteotoxic Stress _gates_from_proteotoxic_stress Cyclic AMP-Response Element Binding Protein _gates_to_cyclic_amp_response_element_binding_protein _gates_from_cyclic_amp_response_element_binding_protein Nuclear Envelope _gates_to_nuclear_envelope _gates_from_nuclear_envelope Apoptosis _gates_to_apoptosis
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Experiment #00000035

What changes in a person's voice occur prior to Amyotrophic Lateral Sclerosis onset that may be useful as a non-clinical (or clinical if possible) early detection of the disease?

Motor Neuron Disease _gates_from_motor_neuron_disease Muscle Weakness _gates_to_muscle_weakness _gates_from_muscle_weakness Vocal Cord Dysfunction _gates_to_vocal_cord_dysfunction Quantitative Analysis _gates_from_quantitative_analysis Biomarkers
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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 #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 #00000023

Does misfolded TDP43 affect Retinal Ganglion Cell STMN2 ability to repair in a similar way as what how it was shown to affect motor neurons with cryptic mis-splicing?

TDP-43 pathology _gates_from_tdp_43_pathology RNA Splicing _gates_to_rna_splicing _gates_from_rna_splicing Stathmin 2 _gates_to_stathmin_2 Vitreous Body _gates_to_vitreous_body DNA-Binding Protein-43
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Experiment #00000019

What is the role of 3-indolepropionic acid within the body, and what foods or nutrients may help replenish it if deficient?

Edible Grain _gates_from_edible_grain Clostridium sporogenes _gates_to_clostridium_sporogenes Gastrointestinal Microbiome _gates_from_gastrointestinal_microbiome 3-indolepropionic acid _gates_to_3_indolepropionic_acid _gates_from_3_indolepropionic_acid Signal Transduction
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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 #00000016

Analyze the potential for zinc-binding competition between synaptic transporters (e.g., SLC39A8, ZnT3) and ALS-associated proteins (RGNEF, TDP-43) in the RGC-thalamic axis. Can this competition explain the coexistence of RGC excitotoxicity and STMN2 depletion in clinical samples?

TAR DNA-Binding Protein 43 _gates_from_tar_dna_binding_protein_43 Stathmin 2 _gates_to_stathmin_2 SLC39A8 protein, human _gates_from_slc39a8_protein__human Zinc _gates_to_zinc Excitotoxicity _gates_from_excitotoxicity
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Experiment #00000007

Simply put, we still don’t know why neurons are dying in ALS, and why motor neurons die while other types of neurons don’t. Even for genetic forms c9orf72 familial ALS, why is it that the mutation is in every cell but the motor neurons are dying ie have increased susceptibility?

Axonal Transport _gates_from_axonal_transport Motor Neuron Disease _gates_to_motor_neuron_disease C9orf72 Repeat Expansion _gates_from_c9orf72_repeat_expansion Dipeptide Repeats _gates_to_dipeptide_repeats _gates_from_dipeptide_repeats VAPB protein, human
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Experiment #00000005

What are the biomarker differences in TDP-43 proteinopathy within the cerebellum and retina when comparing Sporadic Amyotrophic Lateral Sclerosis and c9orf72 affected Familial Amyotrophic Lateral Sclerosis? Are there any mutually exclusive biomarkers that can be deduced?

C9orf72 expansion _gates_from_c9orf72_expansion Dipeptide Repeats _gates_to_dipeptide_repeats _gates_from_dipeptide_repeats Microglia _gates_to_microglia C9orf72 Protein _gates_from_c9orf72_protein Cerebellum
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