# Astaxanthin as a neuroprotective modulator of synaptic plasticity, learning, and memory: mechanistic insights and therapeutic perspectives in neurodegenerative aging

**Authors:** Fan Guo, Jiapei Chi

PMC · DOI: 10.3389/fnagi.2025.1737001 · Frontiers in Aging Neuroscience · 2026-02-10

## TL;DR

Astaxanthin shows promise as a neuroprotective compound that may help maintain cognitive function and delay neurodegenerative diseases during aging.

## Contribution

This review integrates current evidence on astaxanthin's mechanisms and therapeutic potential in neurodegenerative aging.

## Key findings

- Astaxanthin mitigates oxidative stress and regulates mitochondrial function in neurodegenerative models.
- It modulates neuroinflammatory signaling and promotes neurogenesis and synaptic remodeling.
- Astaxanthin influences molecular pathways underlying cognitive function and plasticity.

## Abstract

Astaxanthin (AST), a xanthophyll carotenoid derived from microalgae and marine organisms, has emerged as a potent neuroprotective compound with remarkable antioxidant and anti-inflammatory properties. Growing evidence indicates that AST can modulate multiple molecular and cellular pathways involved in neuronal survival, synaptic plasticity, learning, and memory, particularly in the context of neurodegenerative aging. This review provides an up-to-date and integrative overview of current evidence regarding AST’s mechanisms of action across experimental and preclinical models of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. We highlight its role in mitigating oxidative stress, regulating mitochondrial function, modulating neuroinflammatory signaling, and promoting neurogenesis and synaptic remodeling. Furthermore, we discuss how AST influences key molecular pathways that underlie cognitive function and plasticity. The translational potential of AST as a therapeutic and preventive agent is critically evaluated, alongside its pharmacokinetic challenges, bioavailability, and safety profile in aging populations. Finally, we identify current research gaps and propose future directions toward harnessing AST for promoting cognitive resilience and delaying the progression of neurodegenerative disorders. Collectively, the evidence supports AST as a promising candidate for maintaining neuronal health and cognitive function during brain aging.

## Linked entities

- **Chemicals:** astaxanthin (PubChem CID 5281224)
- **Diseases:** Alzheimer’s disease (MONDO:0004975), Parkinson’s disease (MONDO:0005180), Huntington’s disease (MONDO:0007739)

## Full-text entities

- **Genes:** Psen2 (presenilin 2) [NCBI Gene 19165] {aka ALG-3, Ad4h, Alg3, PS-2, PS2, Psnl2}, Mmp13 (matrix metallopeptidase 13) [NCBI Gene 17386] {aka Clg, MMP-13, Mmp1}, Creb1 (cAMP responsive element binding protein 1) [NCBI Gene 12912] {aka 2310001E10Rik, 3526402H21Rik, Creb, Creb-1}, Gma3 (granulocyte macrophage antigen 3) [NCBI Gene 110204] {aka Gm-3, Gm3}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Bace1 (beta-site APP cleaving enzyme 1) [NCBI Gene 23821] {aka ASP2, Bace}, Foxp3 (forkhead box P3) [NCBI Gene 20371] {aka JM2, scurfin, sf}, Ppara (peroxisome proliferator activated receptor alpha) [NCBI Gene 19013] {aka 4933429D07Rik, Nr1c1, PPAR-alpha, PPARalpha, Ppar}, Slc17a5 (solute carrier family 17 (anion/sugar transporter), member 5) [NCBI Gene 235504] {aka 4631416G20Rik, 4732491M05, AST, ISSD, NSD, SD}, Mog (myelin oligodendrocyte glycoprotein) [NCBI Gene 17441] {aka B230317G11Rik}, Syp (synaptophysin) [NCBI Gene 20977] {aka A230093K24Rik, Syn, p38}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, Prdx6-ps2 (peroxiredoxin 6 pseudogene 2) [NCBI Gene 384001] {aka Aop2-rs2, GPx*, Prdx6-rs2}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Renbp (renin binding protein) [NCBI Gene 19703] {aka Age, Rnbp}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, B3galt4 (UDP-Gal:betaGlcNAc beta 1,3-galactosyltransferase, polypeptide 4) [NCBI Gene 54218] {aka Gal-T2, Galt2}, Snap25 (synaptosomal-associated protein 25) [NCBI Gene 20614] {aka Bdr, GENA70, SNAP-25, SUP, sp}, Lrp1 (low density lipoprotein receptor-related protein 1) [NCBI Gene 16971] {aka A2mr, CD91, Lrp, b2b1554Clo}, Pdgfra (platelet derived growth factor receptor, alpha polypeptide) [NCBI Gene 18595] {aka CD140a, Pdgfr-2}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, Ntrk2 (neurotrophic tyrosine kinase, receptor, type 2) [NCBI Gene 18212] {aka GP145-TrkB/GP95-TrkB, Tkrb, trk-B, trkB}, Dlg4 (discs large MAGUK scaffold protein 4) [NCBI Gene 13385] {aka Dlgh4, PSD-95, PSD95, SAP90, SAP90A}, St8sia1 (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1) [NCBI Gene 20449] {aka 9330109E03Rik, GD3S, Sia-T, Siat8, Siat8a}, Adam10 (a disintegrin and metallopeptidase domain 10) [NCBI Gene 11487] {aka 1700031C13Rik, MADM, kuz, kuzbanian}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, Ppargc1a (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha) [NCBI Gene 19017] {aka A830037N07Rik, Gm11133, PGC-1, PPARGC-1-alpha, Pgc-1alpha, Pgc1}, Lrrk2 (leucine-rich repeat kinase 2) [NCBI Gene 66725] {aka 4921513O20Rik, 9330188B09Rik, D630001M17Rik, Gm927, cI-46}, Spag5 (sperm associated antigen 5) [NCBI Gene 54141] {aka D11Bhm180e, Deepest, MAP126, Mastrin, S17}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Apoa1 (apolipoprotein A-I) [NCBI Gene 11806] {aka Alp-1, Apoa-1, Brp-14, Ltw-1, Lvtw-1, Sep-1}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], St3gal5 (ST3 beta-galactoside alpha-2,3-sialyltransferase 5) [NCBI Gene 20454] {aka 3S-T, Siat9, [a]2}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, Mbp (myelin basic protein) [NCBI Gene 17196] {aka Hmbpr, golli-mbp, jve, mld, shi}, Snca (synuclein, alpha) [NCBI Gene 20617] {aka NACP, alpha-Syn, alphaSYN}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Sirt1 (sirtuin 1) [NCBI Gene 93759] {aka SIR2L1, Sir2, Sir2a, Sir2alpha}, Psen1 (presenilin 1) [NCBI Gene 19164] {aka Ad3h, PS-1, PS1, S182}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, Bax (BCL2-associated X protein) [NCBI Gene 12028], Ache (acetylcholinesterase) [NCBI Gene 11423], Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Abca1 (ATP-binding cassette, sub-family A member 1) [NCBI Gene 11303] {aka ABC-1, Abc1}, Th (tyrosine hydroxylase) [NCBI Gene 21823], Hmox1 (heme oxygenase 1) [NCBI Gene 15368] {aka D8Wsu38e, HO-1, HO1, Hemox, Hmox, Hsp32}, Gls2 (glutaminase 2 (liver, mitochondrial)) [NCBI Gene 216456] {aka A330074B06Rik, GA, GLS, Lga}
- **Diseases:** amyloid (MESH:C000718787), dementia (MESH:D003704), Lewy (MESH:D018827), neuronal damage (MESH:D009410), experimental autoimmune encephalomyelitis (MESH:D004681), depression (MESH:D003866), neuronal apoptosis (MESH:D065703), Cognitive deficits (MESH:D003072), dopaminergic (MESH:D009422), memory deficits (MESH:D008569), motor (MESH:D000068079), synaptic dysfunction (MESH:C536122), MS (MESH:D009103), muscular rigidity (MESH:D009127), autoimmune-mediated demyelinating disorder (MESH:D003711), impairments in brain function (MESH:D001927), death (MESH:D003643), nerve damage (MESH:D000080902), bradykinesia (MESH:D018476), resting tremors (MESH:D014202), hippocampal damage (MESH:D000092223), mitochondria (MESH:C564971), cerebrovascular disease (MESH:D002561), cytotoxic (MESH:D064420), cardiovascular diseases (MESH:D002318), brain inflammation (MESH:D004660), gastrointestinal discomfort (MESH:D005767), diabetic retinopathy (MESH:D003930), slowed (MESH:D012897), oligodendrocyte damage (MESH:D056784), neurofibrillary tangle (MESH:D055956), motor deficits (MESH:D009461), spinal cord injury (MESH:D013119), neuroblastoma (MESH:D009447), pain (MESH:D010146), sleep disturbances (MESH:D012893), PD (MESH:D010300), skin injury (MESH:D000069836), Mitochondrial dysfunction (MESH:D028361), Neurodegeneration (MESH:D019636), injury (MESH:D014947), gastric ulcers (MESH:D013276), chronic inflammation (MESH:D007249), loss (MESH:D016388), metabolic syndrome (MESH:D024821), cortex (MESH:D000303), behavioral deficits (MESH:D019958), skin pigmentation (MESH:D010859), Lewy bodies (MESH:D020961), anxiety (MESH:D001007), Neuroinflammation (MESH:D000090862), AD (MESH:D000544), neurotoxicity (MESH:D020258), Huntington's diseases (MESH:D006816), muscle weakness (MESH:D018908), sensory disturbances (MESH:D012678), cancer (MESH:D009369)
- **Chemicals:** AST (MESH:C005948), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MESH:D015632), beta-carotene (MESH:D019207), lipid (MESH:D008055), alpha-tocopherol (MESH:D024502), ATP (MESH:D000255), Evans blue (MESH:D005070), polyene (MESH:D011090), rotenone (MESH:D012402), GSH (MESH:D005978), AlCl3 (MESH:D000077410), peroxynitrite (MESH:D030421), serotonin (MESH:D012701), DMSO (MESH:D004121), paraquat (MESH:D010269), ROS (MESH:D017382), DHA (MESH:C027493), calcium (MESH:D002118), Dopamine (MESH:D004298), gangliosides (MESH:D005732), polyunsaturated fatty acids (MESH:D005231), (3R,3'S) (-), superoxide (MESH:D013481), donepezil (MESH:D000077265), fatty acids (MESH:D005227), malondialdehyde (MESH:D008315), catecholamines (MESH:D002395), scopolamine (MESH:D012601), CL-82198 (MESH:C000633572), nitrite (MESH:D009573), bexarotene (MESH:D000077610), acetylcholine (MESH:D000109), streptozotocin (MESH:D013311), vitamin A (MESH:D014801), galantamine (MESH:D005702), Luxol Fast Blue (MESH:C018588), NAM (MESH:D009536), Carotenoids (MESH:D002338), nitric oxide (MESH:D009569), cholesterin (MESH:D002784), beta-ionone (MESH:C008157), probucol (MESH:D011341), oxygen (MESH:D010100), cuprizone (MESH:D003471), DPPH (MESH:C004931), carbons (MESH:D002244), MDA (MESH:D015104), vitamin E (MESH:D014810)
- **Species:** Penaeus vannamei (Pacific white shrimp, species) [taxon 6689], Haematococcus lacustris (species) [taxon 44745], Danio rerio (leopard danio, species) [taxon 7955], Rodentia (rodent, order) [taxon 9989], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019), /6J — Homo sapiens (Human), Cutaneous melanoma, Cancer cell line (CVCL_W797), PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), SK-N-SH — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0531)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12929448/full.md

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12929448/full.md

## References

75 references — full list in the complete paper: https://tomesphere.com/paper/PMC12929448/full.md

---
Source: https://tomesphere.com/paper/PMC12929448