Search Results for "unfolded protein response"

Experiment #00000076

Nanoplastic-induced lysosomal membrane remodeling may sequester WDR44, creating a 'hotspot' for α-synuclein aggregation initiation.

Nanoplastics internalization _gates_from_nanoplastics_internalization Lysosomal accumulation _gates_to_lysosomal_accumulation _gates_from_lysosomal_accumulation Lysosomal Membranes _gates_to_lysosomal_membranes WDR44 _gates_from_wdr44 WDR44 protein

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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 #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 #00000068

ALS; FUS; STMN2; TDP-43; protein translation; stress granule

Cell Nucleus _gates_from_cell_nucleus RNA Splicing _gates_to_rna_splicing _gates_from_rna_splicing Protein Biosynthesis _gates_to_protein_biosynthesis _gates_from_protein_biosynthesis Motor Neuron Disease _gates_to_motor_neuron_disease

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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 #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 #00000055

If the RGNEF NF 242 Terminal loses its functional ability to agitate or compete with TDP-43, perhaps from misfolding or sequestration, could it cause the TDP-43 proteinopathy seen in the retina, post-mortem, in Sporadic Amyotrophic Lateral Sclerosis patients, if the RGNEF failures were localized in the retina?

RGNEF/NF242 _gates_from_rgnef_nf242 TDP-43 _gates_to_tdp_43 Rho Guanine Nucleotide Exchange Factor _gates_from_rho_guanine_nucleotide_exchange_factor TDP-43 Proteinopathies _gates_to_tdp_43_proteinopathies Amyotrophic Lateral Sclerosis _gates_from_amyotrophic_lateral_sclerosis

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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 #00000051

Is TDP-43 proteinopathy associated with toxoplasmosis?

Datasets as Topic _gates_from_datasets_as_topic Toxoplasmosis or Toxoplasma gondii _gates_to_toxoplasmosis_or_toxoplasma_gondii TAR DNA-Binding Protein 43 _gates_from_tar_dna_binding_protein_43 _gates_to_datasets_as_topic Toxoplasmosis _gates_from_toxoplasmosis Not Found

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Experiment #00000048

The ALS-T2D comorbidity is driven by a bidirectional, exosome-mediated proteostatic collapse. Peripheral tissues (muscle, pancreas) dictate CNS TDP-43 stability via exosomal miRNAs (miR-126a-5p) and glucose-dependent modifications (O-GlcNAcylation). Conversely, pharmacological activation of ubiquitin-peptidases (e.g., Acarbose targeting USP46) or restitution of glycolytic cofactors (F2,6BP) represent novel, cross-disciplinary therapeutic targets capable of halting systemic proteinopathy.

Diabetes Mellitus, Type 2 _gates_from_diabetes_mellitus__type_2 Extracellular Vesicles _gates_to_extracellular_vesicles _gates_from_extracellular_vesicles DNA-Binding Proteins _gates_to_dna_binding_proteins _gates_from_dna_binding_proteins Amyotrophic Lateral Sclerosis _gates_to_amyotrophic_lateral_sclerosis

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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 #00000042

#PITRM1 #ALS #Microglia #Mitochondria

PITRM1 protein, human _gates_from_pitrm1_protein__human Unfolded Protein Response _gates_to_unfolded_protein_response Mitochondrial Stress _gates_from_mitochondrial_stress DNA, Mitochondrial _gates_to_dna__mitochondrial _gates_from_dna__mitochondrial Neuroinflammation

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Experiment #00000041

What is the biological/molecular pathway that causes sarcopenia with the scope of COPD? Do the quads serve as a pathological progression indicator?

Pulmonary Disease, Chronic Obstructive _gates_from_pulmonary_disease__chronic_obstructive Systemic Inflammatory Response Syndrome _gates_to_systemic_inflammatory_response_syndrome _gates_from_systemic_inflammatory_response_syndrome Signal Transduction _gates_to_signal_transduction _gates_from_signal_transduction Muscular Atrophy _gates_to_muscular_atrophy

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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 #00000037

How does karyoptosis occur compared to apoptosis? SOD1 seems to be associated with apoptosis in some ALS phenotypes, but is SOD1 associated with ALS pathological karyoptosis as well?

Proteotoxic stress _gates_from_proteotoxic_stress p38 kinase signaling _gates_to_p38_kinase_signaling _gates_from_p38_kinase_signaling Apoptosis _gates_to_apoptosis Superoxide Dismutase-1 _gates_from_superoxide_dismutase_1 Karyoptosis (LaminB1 phosphorylation)

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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 #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 #00000024

If RGNEF fails agitate and regulate TDP-43 at the RGNEF NF242 Terminal, does this cause TDP-43 propteinopathy?

Protein Interaction Mapping _gates_from_protein_interaction_mapping RNA Stability _gates_to_rna_stability Peptide Fragments _gates_from_peptide_fragments RNA Recognition Motif _gates_to_rna_recognition_motif Metabolic stress _gates_from_metabolic_stress

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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 #00000022

Do Bulbar Amyotrophic Lateral Sclerosis patients have TDP43 proteinopathy in cochlear/spiral ganglion post mortem?

Ubiquilin-1 _gates_from_ubiquilin_1 TDP-43 Proteinopathies _gates_to_tdp_43_proteinopathies _gates_from_tdp_43_proteinopathies Amyotrophic Lateral Sclerosis _gates_to_amyotrophic_lateral_sclerosis Disease Models, Animal _gates_from_disease_models__animal Cochlear Nucleus

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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 #00000015

Given that schizophrenia is characterized by a deficit in the attenuation of sensory input via corollary discharge, how might pathologically elevated RGC signaling—potentially caused by synaptic glutamate overflow without zinc modulation—interfere with the thalamic integration of extra-retinal CD signals to effectively reverse the predictive timing of visual stability?

SLC39A8 Protein _gates_from_slc39a8_protein Zinc Deficiency _gates_to_zinc_deficiency _gates_from_zinc_deficiency Glutamic Acid _gates_to_glutamic_acid _gates_from_glutamic_acid Thalamus _gates_to_thalamus

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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 #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 #00000006

Does existing in vitro data show that Quercetin-induced autophagy can successfully degrade DUX4 or its downstream misfolded proteins?

Quercetin _gates_from_quercetin Autophagy _gates_to_autophagy _gates_from_autophagy Misfolded Proteins _gates_to_misfolded_proteins _gates_from_misfolded_proteins DUX4 _gates_to_dux4

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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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PathMap Literature Based Discovery Engine

Guaranteed to find unpublished literature based discoveries.

Nanoplastic-induced lysosomal membrane remodeling may sequester WDR44, creating a 'hotspot' for α-synuclein aggregation initiation.

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.

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

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

ALS; FUS; STMN2; TDP-43; protein translation; stress granule

Frontotemporal dementia; Splicing; TDP-43; Transcriptomics.

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?

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

Sarcopenia and Amyotrophic Lateral Sclerosis: Biological Pathways and Analysis

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

Is TDP-43 proteinopathy associated with toxoplasmosis?

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

#PITRM1 #ALS #Microglia #Mitochondria

What is the biological/molecular pathway that causes sarcopenia with the scope of COPD? Do the quads serve as a pathological progression indicator?

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?

How does karyoptosis occur compared to apoptosis? SOD1 seems to be associated with apoptosis in some ALS phenotypes, but is SOD1 associated with ALS pathological karyoptosis as well?

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?

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?

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?

If RGNEF fails agitate and regulate TDP-43 at the RGNEF NF242 Terminal, does this cause TDP-43 propteinopathy?

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?

Do Bulbar Amyotrophic Lateral Sclerosis patients have TDP43 proteinopathy in cochlear/spiral ganglion post mortem?

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?

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?

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?

Does existing in vitro data show that Quercetin-induced autophagy can successfully degrade DUX4 or its downstream misfolded proteins?

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?

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