# Emerging Roles, Mechanisms, and Therapeutic Potential of Thyroid Hormones in Neurodegenerative Diseases: A Review

**Authors:** Xin’ai Li, Zhe Li, Manna Sun, Yunlong Du, Han Bai, Xiaoheng Chen, Junhui Wang

PMC · DOI: 10.3390/brainsci16020229 · Brain Sciences · 2026-02-14

## TL;DR

This review explores how thyroid hormones may influence and potentially treat neurodegenerative diseases like Alzheimer’s, Parkinson’s, and multiple sclerosis.

## Contribution

The paper provides a detailed review of thyroid hormone mechanisms and therapeutic potential in three major neurodegenerative diseases.

## Key findings

- Thyroid hormones may protect neurons and reduce neurodegeneration through mechanisms like neuroprotection and anti-inflammatory effects.
- Thyroid hormone analogs and TRH show promise in preclinical and clinical studies for treating Alzheimer’s, Parkinson’s, and multiple sclerosis.
- Thyroid hormones are linked to oxidative stress and inflammatory responses in neurodegenerative diseases.

## Abstract

Thyroid hormones (THs) are master controllers in the endocrine system and have drawn considerable attention from the research community due to their associations with neurodegenerative diseases as well. In this review article, we present a comprehensive summary of the physiological functions and pathogenic mechanisms of THs in the regulation of several representative neurodegenerative diseases. Our study particularly focuses on Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). AD is the most common cause of dementia, primarily caused by tau protein tangles inside nerve cells and β-amyloid plaques outside, which lead to nerve cell death and brain atrophy. PD is primarily a movement disorder. The degeneration of dopaminergic neurons in the brain impairs the brain’s control over muscle activity. MS is usually considered to be an autoimmune demyelinating disease, but it has been found that MS also presents with secondary neurodegenerative pathology, including axonal loss and neuronal damage. In this review, the effects of TH on the pathogeneses of AD, PD, and MS are discussed in detail, with a focus on the following potential mechanisms: neuroprotection, neurogenesis, oxidative stress, and inflammatory response. In addition, we conduct an in-depth review of the possible clinical applications of TH, TH analogs, and thyrotropin-releasing hormone (TRH) in the treatment of AD, PD, and MS based on recent preclinical and clinical studies. By integrating experimental, clinical, and epidemiological results on the effects of TH on neurodegeneration, the present review constructs a theoretical basis for the involvement of TH in the pathogeneses of these diseases in detail. We believe that this basis will be useful for clinical diagnosis and treatment.

## Linked entities

- **Diseases:** Alzheimer’s disease (MONDO:0004975), Parkinson’s disease (MONDO:0005180), multiple sclerosis (MONDO:0005301)

## Full-text entities

- **Genes:** YOD1 (YOD1 deubiquitinase) [NCBI Gene 55432] {aka DUBA-8, DUBA8, HIN-7, OTUD2, PRO0907}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, Gsk3b (glycogen synthase kinase 3 beta) [NCBI Gene 56637] {aka 7330414F15Rik, 8430431H08Rik, GSK-3, GSK-3beta, GSK3}, HTT (huntingtin) [NCBI Gene 3064] {aka HD, IT15, LOMARS}, NKX2-1 (NK2 homeobox 1) [NCBI Gene 7080] {aka BCH, BHC, NK-2, NKX2.1, NKX2A, NMTC1}, CBS (cystathionine beta-synthase) [NCBI Gene 875] {aka HIP4}, TSHR (thyroid stimulating hormone receptor) [NCBI Gene 7253] {aka CHNG1, LGR3, hTSHR-I}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], TRIB1 (tribbles pseudokinase 1) [NCBI Gene 10221] {aka C8FW, GIG-2, GIG2, SKIP1, TRB-1, TRB1}, SHH (sonic hedgehog signaling molecule) [NCBI Gene 6469] {aka HHG1, HLP3, HPE3, MCOPCB5, SMMCI, ShhNC}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, TREM2 (triggering receptor expressed on myeloid cells 2) [NCBI Gene 54209] {aka AD17, PLOSL2, TREM-2, Trem2a, Trem2b, Trem2c}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, TRH (thyrotropin releasing hormone) [NCBI Gene 7200] {aka Pro-TRH, TRF}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, PFAS (phosphoribosylformylglycinamidine synthase) [NCBI Gene 5198] {aka FGAMS, FGAR-AT, FGARAT, GATD8, PURL}, TPO (thyroid peroxidase) [NCBI Gene 7173] {aka MSA, TDH2A, TPX}, SLC26A4 (solute carrier family 26 member 4) [NCBI Gene 5172] {aka DFNB4, EVA, PDS, TDH2B}, TRIP6 (thyroid hormone receptor interactor 6) [NCBI Gene 7205] {aka OIP-1, OIP1, TRIP-6, TRIP6i2, ZRP-1}, HPT (hypoparathyroidism) [NCBI Gene 3258] {aka HPTX, HYPX}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, PRL (prolactin) [NCBI Gene 5617] {aka GHA1, pPRL}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, THRSP (thyroid hormone responsive) [NCBI Gene 7069] {aka LPGP1, Lpgp, S14, SPOT14, THRP}, NCOR1 (nuclear receptor corepressor 1) [NCBI Gene 9611] {aka N-CoR, N-CoR1, PPP1R109, TRAC1, hN-CoR}, THRB (thyroid hormone receptor beta) [NCBI Gene 7068] {aka C-ERBA-2, C-ERBA-BETA, ERBA2, GRTH, NR1A2, PRTH}, HYOU1 (hypoxia up-regulated 1) [NCBI Gene 10525] {aka GRP-170, Grp170, HSP12A, IMD59, ORP-150, ORP150}, Th (tyrosine hydroxylase) [NCBI Gene 21823], NRCAM (neuronal cell adhesion molecule) [NCBI Gene 4897] {aka NEDNMS}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, PKM (pyruvate kinase M1/2) [NCBI Gene 5315] {aka CTHBP, HEL-S-30, OIP3, PK3, PKM2, TCB}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, Tshr (thyroid stimulating hormone receptor) [NCBI Gene 22095] {aka hypothroid, hyt, pet}, ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase) [NCBI Gene 25] {aka ABL, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL}, TH (tyrosine hydroxylase) [NCBI Gene 7054] {aka DYT14, DYT5b, TYH}, TRB (T cell receptor beta locus) [NCBI Gene 6957] {aka TCRB, TRB@}, SLC16A2 (solute carrier family 16 member 2) [NCBI Gene 6567] {aka AHDS, DXS128, DXS128E, MCT 7, MCT 8, MCT7}, TTR (transthyretin) [NCBI Gene 7276] {aka AMYLD1, ATTR, CTS, CTS1, HEL111, HsT2651}, FOXO1 (forkhead box O1) [NCBI Gene 2308] {aka FKH1, FKHR, FOXO1A}, F2R (coagulation factor II thrombin receptor) [NCBI Gene 2149] {aka CF2R, HTR, PAR-1, PAR1, TR}, Th (tyrosine hydroxylase) [NCBI Gene 25085] {aka The}, NR4A2 (nuclear receptor subfamily 4 group A member 2) [NCBI Gene 4929] {aka HZF-3, IDLDP, NOT, NURR1, RNR1, TINUR}, DIO1 (iodothyronine deiodinase 1) [NCBI Gene 1733] {aka 5DI, THMA2, TXDI1}, EOMES (eomesodermin) [NCBI Gene 8320] {aka TBR2}, ITGAV (integrin subunit alpha V) [NCBI Gene 3685] {aka CD51, IDNDC, MSK8, VNRA, VTNR}, NCOR2 (nuclear receptor corepressor 2) [NCBI Gene 9612] {aka CTG26, N-CoR2, SMAP270, SMRT, SMRTE, SMRTE-tau}, SLC5A5 (solute carrier family 5 member 5) [NCBI Gene 6528] {aka NIS, TDH1}, DIO2 (iodothyronine deiodinase 2) [NCBI Gene 1734] {aka 5DII, D2, DIOII, SELENOY, SelY, TXDI2}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, Eomes (eomesodermin) [NCBI Gene 316052], SRC (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 6714] {aka ASV, SRC1, THC6, c-SRC, p60-Src}, PAX8 (paired box 8) [NCBI Gene 7849] {aka PAX-8}, PTK2 (protein tyrosine kinase 2) [NCBI Gene 5747] {aka FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71}, TRA (T cell receptor alpha locus) [NCBI Gene 6955] {aka IMD7, TCRA, TRA@}, XBP1 (X-box binding protein 1) [NCBI Gene 7494] {aka TREB-5, TREB5, XBP-1, XBP2}, ADM2 (adrenomedullin 2) [NCBI Gene 79924] {aka AM2, dJ579N16.4}, TG (thyroglobulin) [NCBI Gene 7038] {aka AITD3, TGN}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}
- **Diseases:** transthyretin amyloidosis (MESH:C567782), cognitive deficits (MESH:D003072), neurological impairments (MESH:D009422), movement disorder (MESH:D009069), REM sleep behavior disorder (MESH:D020187), autoimmune demyelinating disease (MESH:D020278), axonal loss (MESH:D012183), synaptic dysfunction (MESH:C536122), dysregulation (MESH:D021081), immune dysregulation (OMIM:614878), neurological deficits (MESH:D009461), metabolic (MESH:D008659), MS (MESH:D009103), genetic diseases (MESH:D030342), thyroid deficiency (MESH:D013966), glucose (MESH:D018149), hormone deficiency (MESH:D004393), cerebral injuries (MESH:D000070625), defects in myelination and oligodendrocyte development (MESH:D002658), fatigue (MESH:D005221), hepatic diseases (MESH:D056486), hypokinetic (MESH:D004401), impaired conversion function (MESH:D003291), system (MESH:D015619), amyloid (MESH:C000718787), dementia (MESH:D003704), hyperthyroidism (MESH:D006980), oncogenesis (MESH:D063646), MASH (MESH:D005234), degeneration of dopaminergic neurons (MESH:D009410), autoimmune thyroid disease (MESH:D013967), Thyroid dysfunction (MESH:D013959), Allan-Herndon-Dudley syndrome (MESH:C537047), Deficiency of TH (MESH:D018382), obesity (MESH:D009765), depression (MESH:D003866), experimental autoimmune encephalomyelitis (MESH:D004681), TBI (MESH:D000070642), toxicity (MESH:D064420), CNS disorders (MESH:D002493), disorders of glucose metabolism (MESH:D044882), Neuroinflammatory (MESH:D000090862), insulin resistance (MESH:D007333), anxiety (MESH:D001007), AD (MESH:D000544), familial amyloid polyneuropathy (MESH:D028227), mental illnesses (MESH:D001523), brain atrophy (MESH:C566985), congenital hypothyroidism (MESH:D003409), hereditary amyloidosis (MESH:D028226), genetic, and inflammatory neurological diseases (MESH:D018746), neurotoxicity (MESH:D020258), cardiomyocyte hypertrophy (MESH:D006984), neuropsychiatric (MESH:C000631768), HD (MESH:D006816), endocrine disorders (MESH:D004700), brain injuries (MESH:D001930), Demyelination (MESH:D003711), hypothalamic dysfunction (MESH:D007027), death (MESH:D003643)
- **Chemicals:** glucose (MESH:D005947), cholesterol (MESH:D002784), iodide (MESH:D007454), magnesium (MESH:D008274), borneol (MESH:C022871), dopamine (MESH:D004298), LT3 (MESH:D014284), glutamate (MESH:D018698), lithium (MESH:D008094), Triac (MESH:C010642), lipid (MESH:D008055), iron (MESH:D007501), Resmetirom (MESH:C588408), iodine (MESH:D007455), thyronines (MESH:D013970), phospholipid (MESH:D010743), tyrosine (MESH:D014443), per- and polyfluoroalkyl substances (MESH:D005466), MIBG (MESH:D019797), fatty acid (MESH:D005227), Sobetirome (MESH:C413355), TG (MESH:D013866), diphenyl-methane (MESH:C010129), Magnesium threonate (MESH:C011369), carveol (MESH:C075856), zinc (MESH:D015032), aromatic amino acid (MESH:D024322), FT3 (-), hydrogen peroxide (MESH:D006861), bisphenol (MESH:C543008), LT4 (MESH:D013974), 3-iodothyronamine (MESH:C487948), TSH (MESH:D013972), L-DOPA (MESH:D007980), H2S (MESH:D006862)
- **Species:** Xenopus laevis (African clawed frog, species) [taxon 8355], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Cercopithecidae (monkey, family) [taxon 9527]
- **Mutations:** F245L

## Full text

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## Figures

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## References

177 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938659/full.md

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Source: https://tomesphere.com/paper/PMC12938659