Ask about this productRelated genes to: ALDH1L1 antibody
- Gene:
- ALDH1L1 NIH gene
- Name:
- aldehyde dehydrogenase 1 family member L1
- Previous symbol:
- FTHFD
- Synonyms:
- 10-fTHF, FDH
- Chromosome:
- 3q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-07-23
- Date modifiied:
- 2019-01-11
Related products to: ALDH1L1 antibody
Related articles to: ALDH1L1 antibody
- Extracellular vesicles (EVs) mediate intercellular transfer of lipids, proteins, and nucleic acids between cell types. We previously showed that astrocyte-derived EVs modulate neuronal mitochondria in vitro. Whether endogenous astrocytic EVs associate with neuronal mitochondria in vivo remained unknown. To address this, we generated an EV reporter mouse, Aldh1l1-Cre; CD9-tGFP, which resulted in fluorescent labeling of astrocyte-derived CD9-positive EVs. Astrocyte-specific expression of CD9-tGFP was verified in brain tissue, where CD9-tGFP-positive particles comprised 13.2% ± 1.6% of total isolated EVs. In primary glial cultures, CD9-tGFP was restricted to astrocytes, localizing to vesicular compartments and cell protrusions (filopodia and cilia); 89.3% ± 2.2% of astrocyte-derived EVs were CD9-tGFP positive. In cortex, hippocampus, and cerebellum, CD9-tGFP was predominantly detected in astrocytic processes co-labeled with glutamate aspartate transporter 1 (GLAST1) and glial fibrillary acidic protein (GFAP), forming contacts with laminin-positive capillaries and parvalbumin-positive neurons. CD9-tGFP-labeled EVs were detected at capillaries and inside neurons, and STED microscopy revealed partial co-localization with neuronal mitochondria. Live-cell spinning disk confocal imaging and AI-assisted proximity analysis confirmed uptake of CD9-tGFP EVs by neuronal cells and cargo enrichment at mitochondria in vitro. Immunoblotting and imaging of isolated mitochondria established physical association with EV-derived CD9-tGFP in vivo, with 3-fold higher CD9-tGFP puncta density on synaptic mitochondria. Together, these findings validate the Aldh1l1-Cre; CD9-tGFP reporter mouse as a tool for tracking astrocyte-derived EVs in vivo and provide evidence of preferential cargo enrichment at synaptic mitochondria. - Source: PubMed
Ren XiaojiaQuadri ZainuddinZhu ZhihuiFu XuZhang LipingBieberich Erhard - The role of Klotho in heart failure (HF) and its underlying metabolic mechanisms remain unclear. This study investigated how Klotho deficiency affects extracellular matrix (ECM) homeostasis and metabolic regulation in post-myocardial infarction HF (MI-HF), with a focus on aldehyde dehydrogenase 1 family member L1 (ALDH1L1). - Source: PubMed
Publication date: 2026/08/31
Zhao BingXiao Chun - Folic acid (FA) supplementation during pregnancy is the commonly accepted treatment to prevent neural tube defects. The mechanism by which FA prevents neural tube defects (NTDs) remains unclear. FA also prevents other developmental malformations, including alcohol-induced malformations in Fetal Alcohol Syndrome models. We show that FA acts through a metabolic link to retinoic acid (RA) signaling. Using a -knockdown model of FA-rescuable NTDs, we show that RA or its precursors equally rescue these defects. Similarly, FA rescues alcohol-induced NTDs in a model previously shown to be rescued by retinoids. We identify the FA-metabolizing enzyme, formyl tetrahydrofolate dehydrogenase (ALDH1L1, FTHFD), encoded by the gene, as essential for this rescue. Mechanistically, FA upregulates expression, thereby increasing RA biosynthesis. Knockdown of ALDH1L1 activity using CRISPR/Cas9 abolishes the FA protective effect. To support these observations, we show that the human ALDH1L1 enzyme converts retinaldehyde to RA, and its overexpression restores neural tube closure in -knockdown embryos when retinaldehyde is provided. At the cellular level, reduced RA signaling results in overproliferation of neural plate precursors and a pathological expansion of the neural tube. ALDH1L1 enables FA to restore normal neural plate proliferation, thereby preventing NTDs. These findings establish ALDH1L1 as an unexpected enzymatic link between FA (vitamin B9) and RA signaling, revealing how FA supplementation safeguards neural development and suggesting opportunities to refine strategies for NTD prevention. - Source: PubMed
Publication date: 2026/07/30
Edri TamirAbbou-Levy TaliCohen DorInácio José MShabtai YehudaPillemer GracielaBelo José AntónioFainsod Abraham - Intracerebral hemorrhage (ICH) leads to significant neuronal loss and glial scar formation, but the regenerative capacity of the adult brain remains limited. Although small-molecule-induced astrocyte-to-neuron (AtN) conversion has shown promise in vitro, in vivo applications-particularly under pathological conditions-are still scarce. We aimed to develop and validate a small-molecule cocktail for inducing astrocyte-to-neuron reprogramming in vivo following ICH. We identified a seven-compound cocktail (DFGKLRV) capable of converting astrocytes into neurons under both physiological and ICH conditions. Using immunostaining, RT‒qPCR, electrophysiology, RNA sequencing, neural circuit tracing, and behavioral assessment, we assessed the identity and functionality of induced neurons. In vivo reprogramming was achieved via continuous intracerebral infusion of the cocktail using osmotic pumps. Lineage tracing with aldehyde dehydrogenase 1 family member L1 (Aldh1l1)-Cre/Rosa-CAG-tdTomato mice confirmed the astrocytic origin of the reprogrammed neurons. Additionally, we monitored ferroptosis dynamics during reprogramming and evaluated the effect of ferroptosis inhibition on conversion efficiency. DFGKLRV successfully reprogrammed astrocytes into functional, electrophysiologically active neurons. This reprogramming was effective both in vitro and in vivo, including in the hemorrhagic brain environment. Pharmacological inhibition of ferroptosis significantly improved reprogramming efficiency. Mechanistically, ferroptosis inhibition promoted astrocyte-to-neuron conversion at least in part through suppression of the TGF-β/SMAD3/SOX9 axis, whereas exogenous TGF-β1 treatment or Sox9 overexpression reversed this pro-reprogramming effect. Our findings demonstrate that the DFGKLRV cocktail enables efficient in vivo astrocyte-to-neuron reprogramming following ICH. Moreover, ferroptosis represents a key regulatory mechanism and potential therapeutic target for enhancing chemical reprogramming strategies. - Source: PubMed
Publication date: 2026/07/29
Wang JingyiChen ShilingLi JiaruiLiu XiaWang JiahuiHuang LiyangNie LuweiWu XuanLi YunjieFeng YangyangLiu NaTang YingxinZhu LingqiangQin ChuanLi GaigaiTang Zhouping - Peripheral nerve injury (PNI) induces neuroinflammatory responses in the spinal cord that contribute to neuropathic pain. While microglial proliferation is a well-established feature of this process, whether spinal astrocytes undergo proliferation after PNI seems to be controversial. In this study, we examined astrocytic proliferative responses using Aldh1l1-GFP transgenic mice subjected to spinal nerve ligation (SNL), combined with immunohistochemical and transcriptomic analyses. SNL elicited a temporally organized glial reaction, characterized by early microglial reactivity followed by delayed astrocytic reactivity marked by increased GFAP expression. Despite pronounced astrocytic reactivity, the number of Aldh1l1-GFP⁺ astrocytes in the spinal dorsal horn remained unchanged across all examined time points, and only negligible colocalization with proliferation markers (Ki67 and EdU) was detected. Consistently, transcriptomic analyses revealed extensive astrocyte-associated transcriptional reprogramming without activation of cell-cycle gene programs after PNI. Minimally proliferative astrocytic responses were observed in additional cranial nerve injury model, partial infraorbital nerve transection (pIONT), in which proliferative responses in medullary dorsal horn were also restricted to microglia. Together, these findings demonstrate that spinal or medullary astrocytes respond to PNI with minimal proliferation (rare colocalization with proliferation markers) and primarily through reactive remodeling rather than cell division, providing direct evidence addressing previous inconsistencies and highlighting astrocytic functional plasticity as a key mechanism contributing to neuropathic pain. - Source: PubMed
Publication date: 2026/06/29
Deng Yu-TaoLiu Qing-YeZheng Xuan-JieBai Xue-HuiZeng Jie-TingJiang Bao-Chun