concept

CALCIUM

Entity Detail — Knowledge Graph Node

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This page aggregates everything SciDEX knows about CALCIUM: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

54Connections

12Hypotheses

0Analyses

24Outgoing

30Incoming

13Experiments

0Debates

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💡 Concept Info

Name	CALCIUM
Key Genes/Proteins	PIEZO1

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

calcium-dysregulation-comparison

mechanism · 6247 words

→

Pathway Diagram

graph TD
    CALCIUM["CALCIUM"]
    CALCIUM -->|"regulates"| Neuroregeneration["Neuroregeneration"]
    CALCIUM -->|"mediates"| Axon_Pathfinding["Axon Pathfinding"]
    CALCIUM -->|"mediates"| Growth_Cone_Motility["Growth Cone Motility"]
    CALCIUM -->|"activates"| CAMK2A["CAMK2A"]
    CALCIUM -->|"activates"| PPP3CA["PPP3CA"]
    CALCIUM -->|"regulates"| Synapse_Formation["Synapse Formation"]
    CALCIUM -->|"regulates"| Synaptic_Plasticity["Synaptic Plasticity"]
    CALCIUM -->|"modulates"| Axonal_Regeneration["Axonal Regeneration"]
    MCU["MCU"] -->|"binds"| CALCIUM
    CALCIUM_ASSOCIATED_PROTEINS["CALCIUM-ASSOCIATED PROTEINS"] -->|"binds"| CALCIUM
    CALCIUM_CHANNELS["CALCIUM CHANNELS"] -->|"regulates"| CALCIUM
    SCABP3["SCABP3"] -->|"binds"| CALCIUM
    ION_PUMPS["ION PUMPS"] -->|"regulates"| CALCIUM
    TNF__["TNF-Alpha"] -->|"modulates"| CALCIUM
    calcium_channels["calcium_channels"] -->|"regulates"| CALCIUM
    aging["aging"] -->|"regulates"| CALCIUM

Outgoing (24)

Target	Relation	Type	Str
Neuroregeneration	regulates	process	0.95
Axon Pathfinding	mediates	process	0.93
Synaptic Plasticity	regulates	process	0.90
Synaptogenesis	regulates	process	0.90
Neurite Outgrowth	regulates	process	0.90
Neurodegeneration	causes	process	0.90
Synaptic Vesicle Exocytosis	associated_with	process	0.90
cellular repair pathways	activates	pathway	0.90
NEURODEGENERATION	involved_in	disease	0.90
Synapse Formation	regulates	process	0.90
Axonal Regeneration	modulates	process	0.88
Neurodegeneration	contributes_to	disease	0.85
Actin Filament Stability	regulates	process	0.85
AMPK	activates	protein	0.85
YAP	activates	protein	0.85
Neuron	modulates	cell_type	0.85
neurodegeneration	contributes_to	phenotype	0.85
ALZHEIMER'S DISEASE	involved_in	disease	0.85
PARKINSON'S DISEASE	involved_in	disease	0.85
Serotonylation	regulates	process	0.80
Neurite Outgrowth	mediates	process	0.80
synaptic_transmission	regulates	phenotype	0.72
synaptic_plasticity	regulates	phenotype	0.72
neurons	regulates	cell_type	0.72

Incoming (30)

Source	Relation	Type	Str
MCU	regulates	gene	0.95
MCU	binds	protein	0.95
Trpml1	mediates	protein	0.90
CALCIUM CHANNELS	regulates	protein	0.90
CALCIUM-ASSOCIATED PROTEINS	binds	protein	0.90
SCABP3	binds	protein	0.90
AGING	associated_with	phenotype	0.90
23583927	renders impermeable	paper	0.90
ION PUMPS	regulates	protein	0.85
AMYLOID	associated_with	protein	0.85
MITOCHONDRIA	regulates	cell_type	0.85
Oxidative Stress	associated_with	process	0.85
PSEN1	regulates	gene	0.80
PSEN1	regulates	gene	0.80
SNCA	modulates	gene	0.80
actin filament stability	modulates	phenotype	0.80
Energy Metabolism	modulates	process	0.80
APOE	modulates	gene	0.75
aging	regulates	phenotype	0.72
calcium_channels	regulates	protein	0.72
endoplasmic_reticulum	regulates	cell_type	0.64
oxidative_stress	regulates	phenotype	0.64
amyloid_beta	regulates	protein	0.64
mitochondria	regulates	cell_type	0.64
huntingtin	regulates	protein	0.64
alpha_synuclein	regulates	protein	0.64
C9ORF72	loss_affects	entity	0.60
PIEZO1	regulates	protein	0.56
HTT	regulates	gene	0.56
SNCA	regulates	gene	0.56

Targeting Hypotheses (12)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Calcium-Dysregulated mPTP Opening as an Alternative mtDNA Re	0.804	neurodegeneration	What are the mechanisms by which gut mic
H1: T-Type Calcium Channel–Driven Calcium Overload and Prote	0.730	neurodegeneration	Entorhinal cortex layer II vulnerability
Spatiotemporal coupling between TRPML1-mediated lysosomal ca	0.705	neurodegeneration	What determines the specificity of calci
Calcium-Dependent S100B Release from Astrocyte End-Feet as a	0.700	-	What blood-brain barrier permeability ch
Lysosomal Calcium Channel Modulation Therapy	0.697	neurodegeneration	Autophagy-lysosome pathway convergence a

SUMO1-Mediated Synaptotagmin-1 SUMOylation at Lys124 Impairs	0.652	neurodegeneration	What are the specific PTM changes in syn
Mitochondrial Calcium Buffering Enhancement via MCU Modulati	0.650	neurodegeneration	Selective vulnerability of entorhinal co
MCU Calcium Overload via MFN2/GRP75/VDAC1 MAM Dysfunction	0.644	neurodegeneration	What upstream mechanisms cause TDP-43 to
ER-Mitochondria Calcium Microdomains Couple Mitophagy and ER	0.636	neurodegeneration	How do different organelle-specific auto
Layer V excitatory neurons show selectively enhanced vulnera	0.632	Alzheimer's disease	SEA-AD Single-Cell Analysis: Cell-Type V
Limited Calcium Release Without Sufficient Cathepsin Efflux	0.580	neurodegeneration	How does controlled lysosomal membrane p
Closed-loop transcranial focused ultrasound to restore hippo	0.551	Alzheimer's disease	Circuit-level neural dynamics in neurode

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (13)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Live-cell microscopy of mitochondria-lysosome contacts and calcium dyn	exploratory	mucolipidosis type IV	0.900	0.00	cultured cells	proposed	N/A
Analysis of MLIV patient fibroblasts for contact dynamics and calcium	clinical	mucolipidosis type IV	0.850	0.00	human patient fibroblasts	proposed	N/A
ER-Golgi Secretory Pathway Dysfunction in PD - Experiment Design	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$7,500,000
Lipid Droplet-Lysosome Axis Therapeutic Testing in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
Validate Mitochondria-Lysosome Contact Site Dysfunction in PD	validation	Parkinson's Disease	0.400	0.50	human	proposed	$2,730,000
Presymptomatic GRN Carrier Intervention Timing — Biomarker-Guided Ther	clinical	Neurodegeneration	0.400	0.50	human	proposed	$5,460,000
TMEM106B Haplotype as Genetic Modifier in FTD — Mechanism and Therapeu	validation	Neurodegeneration	0.400	0.50	human	proposed	$2,730,000
s:** - Test MCU overexpression specifically in layer II neurons in hea	falsification	Neurodegeneration	0.400	0.50	mouse	proposed	$200,000
Exercise-BDNF-Mitophagy Biomarker Study in PD	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Ferroptosis Validation in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$6,550,000
Experiment Design: Metal Ion-Synuclein-Mitochondria Axis in Parkinson'	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$5,460,000
MLCS Quantification in Parkinson's Disease	validation	Parkinson's Disease	0.400	0.50	human	proposed	$2,730,000
Wilson Disease Neurodegeneration: Mechanism and Therapeutic Response	clinical	Neurodegeneration	0.400	0.50	human	proposed	$7,500,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of [PMID:30335591]	Rusmini P, Cortese K, Crippa V, Cristofa	Autophagy	2019	2
Mitochondrial calcium uptake declines during aging and is directly activated by [PMID:39603237]	Gherardi G, Weiser A, Bermont F, Migliav	Cell Metab	2025	1
Cytosolic calcium regulates hepatic mitochondrial oxidation, intrahepatic lipoly [PMID:39153480]	LaMoia TE, Hubbard BT, Guerra MT, Nasiri	Cell Metab	2024	1
Mitochondrial calcium exchange in physiology and disease. [PMID:34698550]	Garbincius JF, Elrod JW	Physiol Rev	2022	1
MCOLN1/TRPML1 finely controls oncogenic autophagy in cancer by mediating zinc in [PMID:33890549]	Qi J, Xing Y, Liu Y, Wang MM, Wei X, Sui	Autophagy	2021	1
Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiqui [PMID:30966861]	["Han X", "Sun S", "Sun Y", "Song Q", "Z	Autophagy	2020	1
Mitochondria-lysosome contacts regulate mitochondrial Ca(2+) dynamics via lysoso [PMID:32703809]	Peng W, Wong YC, Krainc D	Proc Natl Acad Sci U S A	2020	1
Chloroquine modulates antitumor immune response by resetting tumor-associated ma [PMID:29491374]	Chen D, Xie J, Fiskesund R, Dong W, Lian	Nat Commun	2018	1
TRPML1: The Ca((2+))retaker of the lysosome. [PMID:28689729]	Di Paola S, Scotto-Rosato A, Medina DL	Cell Calcium	2018	1
TRPML1 suppresses pulmonary fibrosis by limiting collagen and elastin deposition [PMID:41714729]	Weiden EM, Serianz Z, Klingl Y, Jörs S,	The EMBO journal	2026	0
Social Processing in the Amygdala: Single-Nucleus RNA-Sequencing Reveals Distinc [PMID:41727617]	Dwortz MF, Hofmann HA, Curley JP	Res Sq	2026	0
Ceritinib Induces Mitochondrial Fragmentation in Thyroid Cancer Cells by Targeti [PMID:41805100]	Qin D, Ding W, Wu X, Peng C, Bo Y et al.	Drug Dev Res	2026	0
Deficient Cardiolipin Remodelling Alters Muscle Fibre Composition and Neuromuscu [PMID:41841200]	Matias C, Snider PL, Sierra Potchanant E	J Cachexia Sarcopenia Muscle	2026	0
Zn(2+)-Dependent Modulation of the Mitochondrial Ca(2+) Uniporter Underlies Resv [PMID:41932596]	Xing B, Li X, Wang B, Huang L, Wang Q et	Exp Cell Res	2026	0
SERCA2 Dysfunction Drives Vascular Calcification via Coupling with TSPO-MCU at M [PMID:41932666]	Pi S, Liu W, Zhao J, Chen H, Luo X et al	Pharmacol Res	2026	0
PAC regulates endo-, and exocytosis, and lysosomal-mitochondrial stress signalin [PMID:41559803]	Melek K, Steiner P, Kappel S, Gottschalk	Cell communication and signali	2026	0
A perilysosomal feedforward mechanism regulates starvation-induced calcium signa [PMID:41542926]	Giles J, Sesker A, Gonzalez M, Ferow A,	The FEBS journal	2026	0
Inhibition of Cathepsin B protects against vandetanib-induced hepato-cardiotoxic [PMID:41694587]	["Wu W", "Du J", "Li J", "Zhang S", "Kan	International journal of biolo	2026	0
MCOLN1-mediated PPP3CB activation alleviates neuronal damage by promoting TFEB-d [PMID:41876744]	Liu SQ, Liu YY, Fu XX, Cui PR, Wang X, W	Acta pharmacologica Sinica	2026	0
Metformin alleviates ribociclib-induced lung injury by restoring impaired autoph [PMID:41207516]	["Qiu Y", "Chen J", "Zhang Y", "Shu C",	Toxicology and applied pharmac	2026	0

Debates (0)

Multi-agent debates referencing this entity

No debates reference this entity

Related Research

Hypotheses and analyses mentioning CALCIUM in their description or question text

SUMO1-Mediated Synaptotagmin-1 SUMOylation at Lys124 Impairs Calcium Sensing and

Score: 0.652 · neurodegeneration · 2026-04-16

## Mechanistic Overview SUMO1-Mediated Synaptotagmin-1 SUMOylation at Lys124 Impairs Calcium Sensing and Links Synaptic

Mitochondrial Calcium Buffering Enhancement via MCU Modulation

Score: 0.650 · neurodegeneration · 2026-04-02

## Mechanistic Overview Mitochondrial Calcium Buffering Enhancement via MCU Modulation starts from the claim that modula

MCU Calcium Overload via MFN2/GRP75/VDAC1 MAM Dysfunction

Score: 0.644 · neurodegeneration · 2026-04-21

## Mechanistic Overview MCU Calcium Overload via MFN2/GRP75/VDAC1 MAM Dysfunction starts from the claim that modulating

ER-Mitochondria Calcium Microdomains Couple Mitophagy and ER-Phagy Initiation

Score: 0.636 · neurodegeneration · 2026-04-21

**Molecular Mechanism and Rationale** The hypothesis centers on a sophisticated intracellular signaling network orchest

Layer V excitatory neurons show selectively enhanced vulnerability through dysre

Score: 0.632 · Alzheimer's disease · 2026-04-04

## Mechanistic Overview Layer V excitatory neurons show selectively enhanced vulnerability through dysregulated calcium

Limited Calcium Release Without Sufficient Cathepsin Efflux

Score: 0.580 · neurodegeneration · 2026-04-21

## Mechanistic Overview Limited Calcium Release Without Sufficient Cathepsin Efflux starts from the claim that modulatin

Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscilla

Score: 0.551 · Alzheimer's disease · 2026-04-21

## Mechanistic Overview Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via astroc