DRP1/DNM1L Cancer Research Results

DRP1/DNM1L, DRP1 / DNM1L — mitochondrial fission regulator: Click to Expand ⟱
Source:
Type:

DRP1 / DNM1L

Item Description
Target name DRP1 / DNM1L
Full name Dynamin-related protein 1; Dynamin-1-like protein
Gene DNM1L
Primary function Core GTPase regulator of mitochondrial fission; also involved in peroxisomal division, mitosis-linked mitochondrial remodeling, mitophagy, apoptosis regulation, and mitochondrial quality control.
Target class Mitochondrial dynamics / mitochondrial fission / metabolic stress response target
Main disease logic Pathological DRP1 activation can drive excessive mitochondrial fragmentation, impaired oxidative phosphorylation, ROS production, calcium stress, mitophagy imbalance, inflammatory signaling, and cell survival adaptation.
Preferred modulation direction Inhibit excessive DRP1 activation or disrupt pathological DRP1-FIS1 signaling; avoid complete suppression of basal mitochondrial fission.
Key adaptors / related targets FIS1, MFF, MiD49, MiD51, OPA1, MFN1, MFN2, PINK1, PRKN/Parkin
Major caution DRP1 is required for normal mitochondrial maintenance, mitosis, neuronal function, and stress adaptation. Global inhibition could impair normal mitochondrial quality control.

Cancer relevance

Aspect Cancer relevance Likely Desired Direction
Proliferation Many cancer models show increased DRP1-mediated fission supporting mitochondrial redistribution, mitosis, and rapid growth. Down / inhibit excessive DRP1
Metabolic adaptation DRP1 can support metabolic remodeling, mitochondrial fragmentation, altered oxidative phosphorylation, glycolytic adaptation, and survival under stress. Down in DRP1-dependent tumors
Migration / invasion / metastasis DRP1-driven mitochondrial fission can support motility and invasive behavior by changing mitochondrial distribution and energy availability. Down
Cancer stemness / tumor-initiating cells DRP1 and the DRP1-FIS1 axis are implicated in tumor-initiating cell expansion and aggressive phenotypes in some cancers. Down
Therapy resistance Excessive mitochondrial fission may contribute to resistance to chemotherapy, radiation, oxidative stress, and apoptosis depending on tumor type. Down or context-specific
Apoptosis caveat DRP1 can also participate in apoptosis-associated mitochondrial fragmentation. Therefore, indiscriminate DRP1 blockade could theoretically reduce apoptosis in some contexts. Context-dependent
Database cancer rating High mechanistic relevance; strongest as a mitochondrial-stress, invasion, tumor stemness, and therapy-resistance target. Translational status remains preclinical. Add as cancer target

Alzheimer's disease relevance

Aspect Alzheimer's disease relevance Likely Desired Direction
Aβ toxicity Aβ has been reported to interact with DRP1 and promote excessive mitochondrial fission, ROS generation, energetic failure, and synaptic dysfunction. Down / inhibit excessive DRP1
Tau pathology Hyperphosphorylated tau is linked to abnormal mitochondrial dynamics and may worsen DRP1-associated mitochondrial fragmentation. Down
Synaptic function Excessive DRP1 activation can impair mitochondrial transport, ATP availability, and synaptic maintenance. Down
Oxidative stress DRP1-associated mitochondrial fragmentation can increase ROS and reduce mitochondrial membrane potential and respiratory efficiency. Down
Neuroinflammation Altered DRP1 activation has been linked to mitochondrial dysfunction and inflammatory signaling, including NLRP3-related pathways in AD models. Down / normalize
Therapeutic strategy Selective inhibition of pathological DRP1-FIS1 interaction, such as with P110-like strategies, is more attractive than complete DRP1 inhibition. Normalize fission
Database AD rating High mechanistic relevance; strong preclinical rationale for AD mitochondrial dysfunction, Aβ/tau toxicity, ROS, synaptic failure, and neuroinflammation. No established clinical DRP1-directed AD therapy. Add as AD target

Modulators / tool compounds

Compound / Strategy Mechanism Database Note
P110 peptide Selective inhibitor of pathological DRP1-FIS1 interaction; designed to reduce excessive fission while sparing basal fission. Useful reference tool compound; preclinical, not a general supplement or approved therapy.
Mdivi-1 Historically used as a DRP1/fission inhibitor, but has important off-target effects including mitochondrial complex I inhibition. Use cautiously in database notes; not a clean DRP1-specific probe.
Genetic DNM1L knockdown / inhibition Reduces DRP1 expression or activity and can suppress mitochondrial fission in experimental systems. Mechanistic research tool only.
Targeting DRP1-FIS1 axis Blocks a pathological receptor interaction involved in excessive fission. Probably the most attractive disease-modifying approach for AD and some cancers.

Overall conclusion

In cancer, DRP1 is mainly relevant to proliferation, invasion, tumor-initiating cells, metabolic adaptation, and therapy resistance. In Alzheimer's disease, DRP1 is mainly relevant to excessive mitochondrial fission, Aβ/tau toxicity, oxidative stress, synaptic dysfunction, energetic failure, and neuroinflammation. The preferred therapeutic logic is normalization or selective inhibition of pathological DRP1 activation, especially DRP1-FIS1 signaling, rather than complete blockade of mitochondrial fission.



AD, Alzheimer's Disease: Click to Expand ⟱
In Alzheimer's disease (AD), cholinergic dysfunction (often with reduced acetylcholine tone and impaired choline metabolism) is linked with cortical dysfunction, memory deficit, abnormal cerebral blood flow, task learning difficulty, sleep-cycle disruption, and neurodevelopmental effects (context-dependent).
CORE HALLMARKS / HIGH-CONFIDENCE AXES:
- tau and Aβ, their accumulation in AD brains is known to be a major hallmark.
  In AD, PP2A↓ activity is decreased (reported), contributing to hyperphosphorylated tau accumulation.
  SIRT-1↓ levels in AD brains are associated with accumulation of Aβ and tau (reported).
- glucose metabolism↓ (brain glucose hypometabolism) occurs in AD long before significant clinical signs in many cohorts/models (reported).
- Neuroinflammation / lipid mediator tone (reported): 5-LOX↑ and PGE2↑ (model-/region-dependent).
- Synaptic vulnerability (reported): PSD95↓ in hippocampus and cortex; restoring PSD95 shows cognitive benefits in models.
- Clearance/transport imbalance (reported): IDE↓, NEP↓, LRP1↓, and AEP↑ protein levels in AD brains (reported).

COMMONLY REPORTED DIRECTIONAL CHANGES (model/region/compartment dependent):
- Monoamines (reported): concentrations of 5-HTP↓, 5-HT(seratonin)↓, and 5-HIAA↓ are lower in Alzheimer's patients (varies by region/study).
- Cholinergic system (clinical target): reduction in ACh↓ production; ChAT↓ activity reduced (synthesizes ACh).
- Four key enzymes frequently targeted in AD symptom/adjunct strategies: AChE, BChE, MAOA, MAOB (objective inhibit).
- Neurotrophic tone (reported): BDNF↓ in key regions.
  - Stress can decrease expression of brain-derived neurotrophic factor (BDNF).
- Kinase/protease stress (reported): CDK5↑ hyperactivation; calpain↑ overactivated by increased intracellular Ca²⁺ → p-tau and aggregation.
- Aβ-linked synaptic regulator (reported): STEP↑ upregulated largely due to Aβ oligomer accumulation.
- α-secretase axis (reported): ADAM10↓ downregulated in AD brains.
- Metabolic cofactors (reported): ALC↓ (ALCAR); Homocarnosine↓ (CSF declines with age); possible low Taurine↓ (age-related + dementia reports).
- Ion/glutamate handling (reported): impaired glutamate clearance + depressed Na+/K+ ATPase → cellular ion imbalance risk.
- Aging reduces NAD⁺↓ (in AD depletion may be more severe).
- Mitochondrial capacity axis (reported): PGC-1↓ decreased in Alzheimer’s brains.
- Innate immune DNA-sensing axis (animal): cGAS–STING↑ elevation observed in AD mice and normalized by NR treatment.
- Vascular/structure (reported): a profound change in BBB permeability; progressive brain shrinkage (atrophy).
- Glycation axis (reported): AGEs↑ and RAGE↑ expression.
- cerebrospinal fluid (CSF) TMAO is higher in individuals with MCI and AD dementia compared to cognitively-unimpaired individuals. (gut microbes enzymatically generate trimethylamine (TMA) from choline or l-carnitine).
- AD models and human tissue studies show an imbalance toward mitochondrial fission, involving increased DRP1 and FIS1 and reduced fusion proteins such as MFN1, MFN2, and OPA1. Usually increased or overactive in AD-like pathology

HOMOCYSTEINE / B-VITAMIN AXIS:
- Raised plasma total homocysteine (tHcy)↑ associated with cognitive impairment, AD, or vascular dementia (epidemiology).
  - Homocysteine can build up if vitamin B6, B12, or folate levels are low.
  - Homocysteine and B-vitamin in Cognitive Impairment (VITACOG) study.
  - Vit B6 might be an important B vitamin (often discussed along with B12 and folate).
- Thiamine↓ deficiency produces a cholinergic deficit (well-aligned with AD features).
- Decreased thiamine (B1) in AD may exacerbate Aβ deposition, tau hyperphosphorylation, and oxidative stress (reported).

MICRONUTRIENTS / CAROTENOIDS (reported; compartment-dependent):
- vitamin A↓ and β-carotene↓ lower in some AD cohorts; excess retinol may contribute to osteoporosis risk.
- Diminished circulating vitamin E↓ reported in AD.
- Vitamin B5↓ in multiple brain regions (reported).
- Trace elements: patients with AD reported lower serum Se, Cu, and Zn↓ (serum findings vary by study).
- Brain metals: some studies report higher brain copper↑ and iron↑ in specific regions/structures; compartment and region matter.
  Rosmarinic acid reported to reduce copper-induced neurotoxicity in vitro/in vivo and may interfere with amyloid–copper interactions (preclinical).
- SAMe↓ concentrations in CSF reported in AD.
- MPOD often reduced in AD patients.
- AD brains reported lower levels of lutein↓, zeaxanthin↓, anhydrolutein↓, (VitA)retinol↓, lycopene↓, alpha-tocopherol↓.

RISK CONTEXT:
- Apolipoprotein E4 (ApoE4) genotype is the strongest known genetic risk factor for late-onset AD.
  - One copy of ApoE4: ~3–4× increased risk (range varies by cohort).
  - Two copies: ~8–12× increased risk (range varies).
  - VitK lower in circulating blood of APOE4 carriers (reported).
- Type 2 diabetes, traumatic brain injury, stroke, diet, and above all, aging is the number ONE risk factor.

Treatments / Strategy Targets (high-level):
- Early intervention tends to have a greater positive effect than interventions during middle or late stages.
- BOLD fMRI imaging can be used to observe brain activity via blood oxygen/flow changes.
- Reduce ROS and inflammation in the brain (context-dependent; avoid over-suppressing adaptive signaling).
- Inhibiting acetylcholinesterase (AChE) (which breaks down ACh), e.g., donepezil, rivastigmine.
- Natural AChE inhibitors include: Berberine, Luteolin, Crocetin(saffron), Querctin, TQ
- Natural AChE inhibitors in database (check BBB pass potential).
- MAOB inhibitors, APP inhibitors, PGE2 inhibitors, NLRP3 inhibitors, BACE inhibitors
- BDNF activators, PSD95 activator
- STEP, ADAM10
- Diets with an adequate ratio (5:1) of omega-6:3 (Mediterranean diet).
- Vitamins B1, B6, B12, B9 (folic acid) and D, choline, iron and iodine exert neuroprotective effects (general nutrition framing).
- Antioxidants (vitamins C, E, A, zinc, selenium, lutein and zeaxanthin).
- Fiber may promote gut microbiome diversity influencing brain health.
- Supplementing with NAD⁺ precursors (NR or NMN) improves cognition and reduces amyloid/tau pathologies in AD mice (animal evidence).
- "It is advisable to consume diets with an adequate ratio (5:1) of omega-6:3 fatty acids (Mediterranean diet) ... antioxidants ... role in oxidative stress ... cognition." Nutrition Strategies
- Reduction of cognitive decline may be achieved by following a healthy dietary pattern limiting added sugars while maximizing fish, fruits, vegetables, nuts, seeds.

SeNPs may also be useful as a Drug Delivery System.


Related Pathways to research in this database (products that modulate them):
- neuroprotective, cognitive, memory
- Aβ aggregation, Tau↓, AChE↓, ACh↑, ChAT↑, acetyl-CoA↑, BDNF↑, BACE↓, NLRP3↓, PSD95↑, PGE2↓, homoC↓
- Increasing AntiOxidants: Catalase↑, GSH↑, SOD↑, HO-1↑, to decrease ROS↓
- Lower Inflammation: TNF-α↓, IL1β↓, IL6↓

Natural Products that may benefit AD.
-Some key pathways are highlighted in RED in the following links
Acetyl-L-carnitine, ALA, Apigenin, Anthocyanins Blueberrys, Aromatherapy, Artemisinin, Ashwagandha,
β-carotene(vitamin A), Bacopa monnieri, Baicalein, Baicalin, Berberine, Betulinic acid, Boron, Boswellia (frankincense),
Caffeic acid, Caffeine, Capsaicin, Carnosine, Carnosic acid, Chlorogenic acid, Choline (note U shaped dose curve-target 350mg/day), Chrysin, Cinnamon, CoQ10, Crocetin, Curcumin,
dietMed, dietMet, dietSTF, EGCG, Ellagic acid, Exercise, Ferulic Acid, Fisetin, Flav, FLS, Folic Acid (5-MTHF, L-methylfolate)-reduce homocysteine,
Galantamine, Ginger, Ginkgo biloba, Ginseng,
Honokiol, Huperzine A, hydrogen gas, Lecithin, Lutein, Luteolin, Lycopene,
M-Blu, Moringa oleifera, Mushroom Lion’s Mane, MSM, MCToil, NAD, Naringenin,
PEMF, Piperine, Phenylbutyrate, Phosphatidylserine, Piperlongumine, Potassium, probiotics, Propolis, Pterostilbene,
Quercetin, Resveratrol, Rivastigmine, Rosmaric Acid(reduce copper-induced neurotoxicity), Rutin,
Safflower yellow, Sage, SAMe, selenium, Serotonin, Shankhpushpi, Shikonin, Shilajit/Fulvic Acid, silicon(reduce Alum bioavialability), Silymarin (Milk Thistle) silibinin, Sulforaphane,
Taurine, TQ, Ursolic Acid
Vitamin B1, Vitamin B2, Vitamin B3, Vitamin B5, Vitamin B6, Vitamin B12, Vitamin E, Vitamin D, Vitamin K2
Zeaxanthin, zinc,

Aluminium has a negative impact on cognition but silicon can decrease Alumunium bioavailability, and Vitamin K2 may provide some protection. Example So does RMF

Brain Energy Systems Matrix (AD)

Tier 1–2 as “core metabolic cofactors / redox pools”
Tier 4 as “alternative fuels / bypass strategies”
Tier 5–6 as “capacity + delivery constraints” (often explains why supplements don’t translate)
Tier Rank Node / Lever What it Supports (Bioenergetic Role) Key Enzymes / Targets AD-Relevant Mechanism TSF Evidence Common Constraints / Gotchas
11 Thiamine (B1) / TPP Glucose → acetyl-CoA entry + TCA throughput + NADPH support PDH, α-KGDH, Transketolase (PPP) Addresses cerebral glucose hypometabolism; improves mitochondrial flux; PPP→NADPH supports redox R, G Mechanistic + small clinical Benefit strongest if low status; standard thiamine vs lipophilic derivatives differ
12 Benfotiamine Higher-bioavailability B1 strategy Transketolase ↑; glycation axis ↓ AGE/RAGE burden reduction + metabolic support (model/trial dependent) G Small clinical + mechanistic Not a “rapid” effect; mostly longer-term metabolic/toxicity load reduction
13 Riboflavin (B2) / FAD, FMN ETC redox enzymes + mitochondrial dehydrogenases Complex I/II flavoproteins; many oxidoreductases Supports electron handling; can be limiting in mitochondrial enzyme insufficiency R, G Mechanistic Direct AD cognitive trial support limited; “helps” mostly when deficient or enzyme-limited
14 Niacin forms (B3) → NAD pool NAD+/NADH redox + signaling + repair NAD salvage; sirtuins; PARP substrate NAD decline is an aging/inflammation theme; supports mitochondrial redox capacity R, G Emerging human + mechanistic Different forms behave differently; NAD raising ≠ guaranteed clinical cognition benefit
15 Pantothenic acid (B5) → CoA Acetyl-CoA formation; lipid metabolism; TCA entry CoA biosynthesis; acetylation capacity Foundational for fuel oxidation and acetylation balance G Mechanistic Often overlooked; deficiency uncommon but suboptimal intake can matter in frailty
16 Magnesium ATP handling (Mg-ATP) + enzyme kinetics ATP-dependent enzymes; synaptic function Supports neuronal energy usage + plasticity; deficiency can worsen excitotoxic vulnerability R, G Supportive human + mechanistic Form/absorption variability; renal constraints for supplementation in some patients
21 NAD+ precursors (NR/NMN/NA/NAM) Restores NAD+ availability for redox + signaling NAMPT salvage; sirtuins; PARPs; CD38 Supports mitochondrial function; may improve resilience under oxidative/repair load R, G Animal > human (emerging) NAD “sinks” (CD38/PARP) can dominate; response varies by inflammation/age
22 Alpha-lipoic acid (ALA) Mitochondrial redox cofactor + antioxidant recycling PDH/α-KGDH cofactor; GSH recycling support Improves redox tone and mitochondrial efficiency (signals strongest in metabolic/oxidative phenotypes) R, G Small AD trials + mechanistic “Antioxidant” framing can be misleading—main value is mitochondrial/redox coupling support
23 Glutathione system support Detox + peroxide handling GSH, GPx, GR, NADPH supply (PPP) Reduces oxidative damage load that impairs mitochondria/synapses R, G Mechanistic GSH depends on substrates + NADPH; pushing one component may not fix system
24 Selenium (GPx capacity) Peroxide detox via selenoenzymes Glutathione peroxidases Supports antioxidant enzyme capacity (context-dependent) G Mixed human Narrower safety margin; avoid “more is better” mindset
31 CoQ10 (ubiquinone) ETC electron carrier (I/II→III) + membrane redox Complex I/II→III transfer Supports OXPHOS efficiency; may reduce electron leak under some conditions R, G Limited AD-specific Bioavailability/formulation matters; AD cognition data not robust
32 Cardiolipin / mitochondrial membranes (support axis) ETC supercomplex stability; cristae integrity Inner mitochondrial membrane architecture Membrane integrity affects ETC efficiency and ROS leak G Mechanistic Hard to “target” nutritionally in a clean way; effects indirect
33 Iron / copper homeostasis (burden control) Prevents metal-catalyzed oxidative damage Fenton chemistry burden; metal transport/storage Metal dyshomeostasis can amplify ROS and mitochondrial injury R, G Mechanistic + mixed human “Chelation” is not casually safe; needs careful framing and evidence
41 Ketone utilization (BHB/acetoacetate axis) Alternative brain fuel bypassing glucose bottlenecks MCT1/2 transport; ketolysis enzymes Addresses brain glucose hypometabolism by providing alternate substrate R, G Moderate (human MCI/AD signals exist) GI tolerance and adherence; response varies by genotype/metabolic status
42 Creatine / phosphocreatine shuttle ATP buffering and rapid energy stabilization Creatine kinase system May stabilize energy during stress; supports muscle/functional reserve that impacts cognition indirectly G Limited AD CNS benefit uncertain; stronger for muscle/functional outcomes
43 Acetyl-L-carnitine (ALCAR) Fatty acid oxidation support + acetyl group handling Carnitine shuttle; acetyl-CoA support May support mitochondrial energy and neuronal function (mixed clinical results) R, G Mixed human Benefits heterogeneous; not a universal cognitive improver
44 Medium-chain triglycerides (MCT oil → ketones) Rapid ketone support strategy Hepatic ketogenesis; brain ketone uptake Practical ketone-raising approach for some phenotypes R, G Moderate human GI effects; calorie load; titration matters
51 AMPK → PGC-1α biogenesis axis Mitochondrial number/quality regulation AMPK, PGC-1α, SIRT1 Supports long-term mitochondrial capacity and stress resistance G Mechanistic Most effects are slow; many “activators” are indirect and context-dependent
52 Mitophagy / autophagy quality control Removes damaged mitochondria PINK1/Parkin axis; autophagy machinery Damaged mitochondria drive ROS and energy failure; quality control is protective in theory G Mechanistic Autophagy modulation is double-edged; oversimplified “more autophagy = good” is risky
53 Exercise signaling (the “master cofactor”) Improves vascular + mitochondrial + neurotrophic tone BDNF; insulin sensitivity; AMPK/PGC-1α Most evidence-backed multi-pathway energy intervention for aging brain R, G Strong (human) Adherence/ability constraints; must be individualized
61 Cerebral perfusion / vascular health Fuel + oxygen delivery and waste clearance support Neurovascular unit; endothelial function Vascular dysfunction worsens hypometabolism and inflammation R, G Strong (human) Often upstream of “supplement” efficacy; if delivery is poor, cofactors underperform
62 Sleep / glymphatic clearance Waste clearance & metabolic recovery Glymphatic system; circadian regulation Supports clearance of metabolic byproducts; indirectly supports energy balance G Strong (human) Often neglected; impacts cognition and inflammation strongly
63 Oxygen utilization context (respiratory capacity) Oxidative metabolism support OXPHOS dependence If oxygen delivery/usage is limited, pushing mitochondrial cofactors won’t fully translate R, G Supportive More about system constraints than a “node to supplement”

TSF (Time-Scale Flag): P = 0–30 min, R = 30 min–3 hr, G = >3 hr (adaptation/phenotype). Evidence: "Strong (human)" = consistent clinical/epidemiologic support; "Moderate" = mixed but plausible human signals; "Emerging" = early-stage human; "Mechanistic" = preclinical/biochemical rationale.



Scientific Papers found: Click to Expand⟱
6414- NoProd,    Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease: implications for neuronal damage
- Study, AD, NA
*eff↑, *DRP1/DNM1L↑, *FIS1↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


NA, unassigned ⓘ

DRP1/DNM1L↑, 1,   FIS1↑, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  
Total Targets: 3

Scientific Paper Hit Count for: DRP1/DNM1L, DRP1 / DNM1L — mitochondrial fission regulator
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:38  Cells:%  prod#:%  Target#:1487  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

Home Page