# Klotho Function in Neurogenesis and Oligodendrogenesis: A Mini-Review Update

**Authors:** Isabela Ribeiro Possebom, Geovana Rosa Oliveira dos Santos, Elisa Mitiko Kawamoto

PMC · DOI: 10.1007/s12031-026-02487-z · Journal of Molecular Neuroscience · 2026-02-24

## TL;DR

This review summarizes how the anti-aging protein Klotho supports brain cell development and myelination, potentially offering new ways to treat neurological diseases.

## Contribution

This review synthesizes current knowledge on Klotho's role in neurogenesis and oligodendrogenesis, highlighting its potential as a therapeutic target.

## Key findings

- Klotho promotes adult neurogenesis and neural progenitor cell proliferation.
- Klotho enhances oligodendrocyte differentiation and myelination.
- Klotho modulates cell fate decisions in neurogenesis and oligodendrogenesis.

## Abstract

Klotho is an anti-aging protein with multiple functions in maintaining homeostasis within the central nervous system (CNS). Klotho-induced neurogenesis and oligodendrogenesis play a critical role in myelination, neuroplasticity, and hippocampus-dependent cognition. In this context, the objective of this review is to synthesize well-established information about the mechanisms through which Klotho influences neurogenesis and oligodendrogenesis. Previous studies have demonstrated that Klotho regulates adult neurogenesis, stimulates the proliferation of neural progenitor cells (NPCs), promotes the differentiation of NPCs into neurons, and facilitates neuronal maturation and dendritic arborization. Additionally, Klotho stimulates oligodendrocyte differentiation and maturation, as well as myelination throughout life. The reviewed evidence suggests that Klotho influences cell fate decisions during both development and adulthood and has a modulatory role in neuronal fate determination from embryonic stem cells in neurogenesis and oligodendrogenesis. Therefore, Klotho may represent a promising therapeutic target for neuroprotection, including the prevention of neurodevelopmental and neurodegenerative diseases.

## Linked entities

- **Genes:** CG9701 (uncharacterized protein) [NCBI Gene 39872]

## Full-text entities

- **Genes:** Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, ADAM10 (ADAM metallopeptidase domain 10) [NCBI Gene 102] {aka AD10, AD18, CD156c, CDw156, HsT18717, MADM}, Fgf21 (fibroblast growth factor 21) [NCBI Gene 56636] {aka Fgf8c}, Prkaa2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 78975] {aka Ampk, Ampka2}, Rbfox3 (RNA binding protein, fox-1 homolog (C. elegans) 3) [NCBI Gene 52897] {aka Fox-3, Hrnbp3, NeuN, Neuna60}, Fgf15 (fibroblast growth factor 15) [NCBI Gene 14170] {aka FGF19, Fgf8a}, Grin2b (glutamate receptor, ionotropic, NMDA2B (epsilon 2)) [NCBI Gene 14812] {aka GluN2B, GluRepsilon2, NR2B, Nmdar2b}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345] {aka D630048A14Rik, Ki-67, Ki67}, Sox2 (SRY (sex determining region Y)-box 2) [NCBI Gene 20674] {aka Sox-2, lcc, ysb}, ADAM17 (ADAM metallopeptidase domain 17) [NCBI Gene 6868] {aka ADAM18, CD156B, CSVP, HYPT16, NISBD, NISBD1}, Kl (Klotho) [NCBI Gene 83504], Igf1 (insulin-like growth factor 1) [NCBI Gene 16000] {aka C730016P09Rik, Igf-1, Igf-I}, Chn1 (chimerin 1) [NCBI Gene 108699] {aka 0610007I19Rik, 0710001E19Rik, 1700112L09Rik, 2900046J01Rik, ARHGAP2}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, KL (klotho) [NCBI Gene 9365] {aka HFTC3, KLA}, Gfap (glial fibrillary acidic protein) [NCBI Gene 14580], Nefl (neurofilament light chain) [NCBI Gene 83613] {aka NF-L, NF68, Nfl}, Rbfox3 (RNA binding fox-1 homolog 3) [NCBI Gene 287847] {aka Hrnbp3, Neun, RGD1560070}, Nes (nestin) [NCBI Gene 18008] {aka ESTM46, Ifaprc2, Marc2, RC2}, Fgf23 (fibroblast growth factor 23) [NCBI Gene 64654] {aka Fgf8b}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, KLB (klotho beta) [NCBI Gene 152831] {aka BKL}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], Fgfr4 (fibroblast growth factor receptor 4) [NCBI Gene 14186] {aka Fgfr-4}, KITLG (KIT ligand) [NCBI Gene 4254] {aka DCUA, DFNA69, FPH2, FPHH, KL-1, Kitl}, Kl (klotho) [NCBI Gene 16591] {aka alpha-kl}, 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}, Fgfr1 (fibroblast growth factor receptor 1) [NCBI Gene 14182] {aka Eask, FGFR-I, FLG, Fgfr-1, Flt-2, Fr1}, Klb (klotho beta) [NCBI Gene 83379] {aka betaKlotho}, Dcx (doublecortin) [NCBI Gene 13193] {aka Dbct}
- **Diseases:** type 2 diabetes (MESH:D003924), myelination impairment (MESH:D020279), neurodevelopmental disorders (MESH:D002658), malformations (MESH:C564254), multiple sclerosis (MESH:D009103), frontotemporal dementia (MESH:D057180), memory (MESH:D008569), cognitive and motor dysfunction (MESH:D003072), amyotrophic lateral sclerosis (MESH:D000690), atherosclerosis (MESH:D050197), Myelination (MESH:D003711), ischemic injury (MESH:D017202), infertility (MESH:D007246), cardiovascular diseases (MESH:D002318), osteoporosis (MESH:D010024), obesity (MESH:D009765), developmental defects (MESH:D000094602), gait disturbance (MESH:D020233), NPC (MESH:D052556), volume loss (MESH:D016388), and neurodegenerative diseases (MESH:D019636), inflammatory (MESH:D007249), diabetes (MESH:D003920), cerebral ischemia injury (MESH:D002545), cancer (MESH:D009369), arteriosclerosis (MESH:D001161), neurotoxicity (MESH:D020258), emphysema (MESH:D004646), CKD (MESH:D051436), schizophrenia (MESH:D012559)
- **Chemicals:** calcium (MESH:D002118), glucose (MESH:D005947), bile acid (MESH:D001647), anti- (-), dUTP (MESH:C027078), fatty acid (MESH:D005227), glutamate (MESH:D018698), cuprizone (MESH:D003471), vitamin D (MESH:D014807), phosphate (MESH:D010710)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** MO3.13 — Homo sapiens (Human), Hybrid cell line (CVCL_D357), 3T3-L1 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0123)

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12932406