ALDH1L1 — Aldehyde Dehydrogenase 1 Family Member L1
Overview
ALDH1L1 (Aldehyde Dehydrogenase 1 Family Member L1) is a folate-metabolizing enzyme that catalyzes the oxidation of 10-formyltetrahydrofolate to tetrahydrofolate in the mitochondrial folate pathway. Located on chromosome 3q21.3, ALDH1L1 encodes a 902-amino acid protein with multiple functional domains. The enzyme is highly expressed in the liver and brain, particularly in astrocytes where it serves as a specific marker for mature astrocytes. ALDH1L1 plays a critical role in one-carbon metabolism by generating tetrahydrofolate (THF), which is essential for DNA synthesis, methylation reactions, and cellular redox balance.
The ALDH1L1 gene encodes a mitochondrial enzyme that sits at a crucial intersection of folate metabolism and cellular homeostasis. The enzyme converts 10-formyltetrahydrofolate (10-formyl-THF) to tetrahydrofolate (THF), simultaneously producing NADPH through its aldehyde dehydrogenase activity. This dual function positions ALDH1L1 as a key regulator of one-carbon metabolism that impacts DNA synthesis, methylation capacity, and cellular redox state—all processes critical to neuronal health and implicated in neurodegenerative diseases.
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">ALDH1L1</th></tr>
<tr><td><strong>Gene Symbol</strong></td><td>ALDH1L1</td></tr>
<tr><td><strong>Full Name</strong></td><td>Aldehyde Dehydrogenase 1 Family Member L1</td></tr>
<tr><td><strong>Chromosome</strong></td><td>3q21.3</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td><a href="https://www.ncbi.nlm.nih.gov/gene/108" target="_blank">108</a></td></tr>
<tr><td><strong>OMIM</strong></td><td><a href="https://www.omim.org/entry/600182" target="_blank">600182</a></td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000135917</td></tr>
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/O75459" target="_blank">O75459</a></td></tr>
<tr><td><strong>Protein Name</strong></td><td>Aldehyde dehydrogenase 1 family member L1</td></tr>
<tr><td><strong>Protein Class</strong></td><td>Enzyme (Aldehyde dehydrogenase, formyltransferase)</td></tr>
<tr><td><strong>Cellular Localization</strong></td><td>Mitochondria (matrix)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>Alzheimer's Disease, Parkinson's Disease, Neural Tube Defects, Cancer, Cognitive Impairment</td></tr>
</table>
</div>
Protein Structure and Function
Structural Features
ALDH1L1 is a multi-domain protein with several distinct functional regions:
N-terminal Formyltransferase Domain: Transfers the formyl group from 10-formyl-THF to the aldehyde substrate
Aldehyde Dehydrogenase (ALDH) Domain: Catalyzes oxidation of the formyl group, producing NADPH
Tetrahydrofolate Binding Site: Binds THF for regeneration and release
Mitochondrial Targeting Sequence: N-terminal signal for mitochondrial importCatalytic Mechanism
ALDH1L1 performs a unique two-step catalytic reaction:
Formyl Transfer: The formyltransferase domain transfers the formyl group from 10-formyl-THF to a thiol group on the enzyme, forming a formyl-enzyme intermediate
Oxidation: The ALDH domain oxidizes this intermediate, transferring electrons to NAD+ to form NADPHThis reaction simultaneously:
- Generates tetrahydrofolate (THF) for one-carbon metabolism
- Produces NADPH for biosynthetic reactions and antioxidant defense
Alternative Splicing
The ALDH1L1 gene produces multiple splice variants:
- Full-length ALDH1L1 (902 aa): The canonical mitochondrial enzyme
- ALDH1L1-S: A shorter isoform lacking the mitochondrial targeting sequence, localizing to the cytosol
- ALDH1L1-2: An alternative splice variant with distinct tissue distribution
Folate Cycle
ALDH1L1 occupies a central position in the folate cycle:
Mermaid diagram (expand to render)
NADPH Production
The ALDH1L1 reaction is a significant source of NADPH in mitochondria:
- NADPH is essential for:
- Glutathione reductase (antioxidant defense)
- Ribonucleotide reductase (DNA synthesis)
- Fatty acid synthesis
- Cytochrome P450 reactions
This makes ALDH1L1 crucial for maintaining cellular redox balance, particularly important in neurons with high metabolic demands.
Connection to S-Adenosylmethionine (SAM)
Through generating THF, ALDH1L1 indirectly supports methylation reactions:
THF accepts methyl groups to form 5-methyl-THF
5-methyl-THF donates methyl groups to homocysteine, forming methionine
Methionine is converted to S-adenosylmethionine (SAM)
SAM is the universal methyl donor for DNA, RNA, proteins, and lipidsExpression Patterns
Tissue Distribution
ALDH1L1 exhibits a distinctive expression pattern:
High Expression:
- Liver (hepatocytes)
- Brain (astrocytes)
- Kidney
- Testis
- Oviduct
Moderate Expression:
- Small intestine
- Colon
- Pancreas
- Skeletal muscle
Brain Expression
In the central nervous system, ALDH1L1 is predominantly expressed in:
- Astrocytes: Specifically in mature, differentiated astrocytes
- Bergmann glia (cerebellum)
- Radial glia (developmental)
- Ependymal cells
ALDH1L1 is NOT expressed in:
- [Neurons](/cell-types/neuro- [Microglia](/cell-types/microglia)rocytes
- [Microglia](/cell-types/microglia) Neural stem cells (generally)
This astrocyte-specific expression makes ALDH1L1 one of the most specific astrocyte markers available for research.
Cellular Expression
Within astrocytes, ALDH1L1 localizes to:
- Mitochondrial matrix
- Astrocytic processes
- Perivascular end-feet
- Synaptic surrounding processes
Role in Neurodegenerative Diseases
Alzheimer's Disease
ALDH1L1 and one-carbon metabolism have several connections to Alzheimer's disease:
Folate and Amyloid Metabolism: Folate-dependent metabolism affects amyloid precursor protein (APP) processing and amyloid-beta production [@amyloid_metabolism_2018]. Altered one-carbon metabolism may:
- Influence amyloidogenic processing
- Affect amyloid clearance
- Modulate neuroinflammation
DNA Methylation: Alzheimer's disease is associated with widespread DNA hypomethylation. Folate deficiency reduces SAM availability, impairing methylation capacity [@methylation_2017].
Homocysteine Metabolism: Impaired folate metabolism leads to elevated homocysteine, a risk factor for AD and cognitive decline [@homocysteine_2019].
Tau Pathology: Folate-dependent methylation may influence tau protein post-translational modifications and aggregation [@tau_methylation_2019].
Neuroinflammation: Astrocyte ALDH1L1 supports anti-inflammatory responses through proper folate metabolism and NADPH production.Parkinson's Disease
ALDH1L1 has several connections to Parkinson's disease:
Dopaminergic Neuron Vulnerability: The substantia nigra has high metabolic demands. ALDH1L1-dependent NADPH production may be particularly important for antioxidant defense in these neurons.
Mitochondrial Dysfunction: PD involves mitochondrial complex I deficiency. Folate metabolism supports mitochondrial function through:
- NADPH for mitochondrial antioxidants
- Nucleotide synthesis for mitochondrial DNA
- Methylation for mitochondrial proteins
Levodopa Metabolism: Folate status affects levodopa metabolism and efficacy.
Neuroinflammation: Astrocyte activation in PD may involve ALDH1L1 dysregulation.Other Neurodegenerative Conditions
Amyotrophic Lateral Sclerosis (ALS): Altered one-carbon metabolism has been reported in ALS patients.
Huntington's Disease: Folate metabolism may be affected in HD, with potential therapeutic implications.
Multiple Sclerosis: Demyelination involves altered folate metabolism in astrocytes.
Aging: One-carbon metabolism declines with age, potentially contributing to age-related cognitive decline.Molecular Pathways
ALDH1L1 in astrocytes supports neuronal function through:
Folate Supply: Astrocytes release folate derivatives for neuronal use
NADPH for Antioxidant Defense: Astrocytic NADPH supports both astrocyte and neuronal antioxidant defenses through the glutathione system
Methylation Support: SAM produced in astrocytes supports neuronal methylation reactions
Neurotransmitter Cycling: Proper astrocyte metabolism supports glutamate and GABA cyclingRedox Balance
ALDH1L1-generated NADPH is critical for:
Mermaid diagram (expand to render)
Epigenetic Regulation
Through THF production, ALDH1L1 supports:
- DNA methylation (via SAM)
- Histone methylation
- RNA methylation
- Chromatin remodeling
These epigenetic modifications are crucial for:
- Gene expression regulation
- Neuronal differentiation
- Synaptic plasticity
- Memory formation
Therapeutic Implications
Folate Supplementation
Understanding ALDH1L1 function has led to therapeutic approaches:
Folic Acid Supplementation: Used in AD and PD clinical trials with mixed results
5-Methyltetrahydrofolate (5-MTHF): The active form may be more effective than folic acid
L-methylfolate: A medical food for patients with MTHFR polymorphismsTargeting ALDH1L1
Direct modulation of ALDH1L1 is challenging but potentially valuable:
Activation: Could enhance NADPH production and support antioxidant defense
Inhibition: May have utility in certain cancer contextsChallenges
- Blood-brain barrier penetration
- Individual genetic variation (MTHFR polymorphisms)
- Potential for compensatory mechanisms
- Optimal timing of intervention
ALDH1L1 intersects with several key cellular mechanisms:
- [One-Carbon Metabolism](/mechanisms/one-carbon-metabolism)
- [Astrocyte Function](/cell-types/astrocytes)
- [Folate Metabolism](/mechanisms/folate-metabolism)
- [Mitochondrial Function](/organelles/mitochondria)
- [DNA Methylation](/mechanisms/dna-methylation)
- [Neuroinflammation](/mechanisms/neuroinflammation)
- [Antioxidant Defense](/mechanisms/antioxidant-defense)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Homocysteine Metabolism](/mechanisms/homocysteine-metabolism)
Summary
ALDH1L1 is a folate-metabolizing enzyme and specific astrocyte marker that plays critical roles in one-carbon metabolism, NADPH production, and cellular redox balance. Its astrocyte-specific expression makes it invaluable for research on astrocyte involvement in neurodegeneration, while its enzymatic function connects folate metabolism to DNA synthesis, methylation, and antioxidant defense—all processes fundamental to neuronal health and implicated in AD, PD, and related conditions.
Detailed Mechanisms
Astrocyte Support of Neurons
Astrocytes provide crucial metabolic support to neurons:
Glucose Metabolism: Astrocytes metabolize glucose and share intermediates with neurons
Folate Cycling: Astrocytes take up folate, metabolize it through ALDH1L1, and release derivatives for neurons
Glycogen Storage: Astrocytes store glycogen for times of high neuronal demand
Potassium Buffering: Astrocytes take up excess extracellular potassium
Water Homeostasis: Astrocyte water channels help maintain extracellular balanceThe mitochondrial folate pathway:
Import: Folate is imported into mitochondria via specific transporters
Activation: Mitochondrial enzymes convert folate to 10-formyl-THF
ALDH1L1 Reaction: ALDH1L1 converts 10-formyl-THF to THF, producing NADPH
Output: THF is exported to the cytosol for further metabolismThis mitochondrial folate cycle is distinct from the cytosolic one-carbon pool and has specific functions in:
- Mitochondrial DNA synthesis (dTMP)
- Mitochondrial NADPH production
- Mitochondrial protein methylation
- Iron-sulfur cluster biosynthesis
Folate and Neurodevelopment
During neural development, folate is essential for:
Neural Tube Closure: Folate prevents neural tube defects
Proliferation: Rapid cell division requires folate for nucleotide synthesis
Differentiation: Epigenetic regulation via methylation supports differentiation
Migration: Folate-dependent processes affect neuronal migration
Synaptogenesis: Proper synapse formation requires folate metabolismMaternal folate status during pregnancy affects:
- Neural tube closure
- Brain development
- Long-term neurocognitive outcomes
Folate Deficiency Consequences
When ALDH1L1 function or folate availability is compromised:
Reduced DNA Synthesis: Impaired dTMP production affects DNA replication and repair
Methylation Defects: Reduced SAM leads to DNA hypomethylation
Oxidative Stress: NADPH deficiency compromises antioxidant defenses
Homocysteine Accumulation: Elevated homocysteine is neurotoxic
Impaired Mitochondrial Function: Reduced mitochondrial DNA synthesisNeuroinflammation and ALDH1L1
Astrocyte activation (reactive astrogliosis) involves changes in ALDH1L1:
Upregulation in Some Contexts: Activated astrocytes may increase ALDH1L1
Downregulation in Others: Chronic inflammation may suppress ALDH1L1
Functional Consequences: Altered ALDH1L1 affects inflammatory responses
Therapeutic Implications: Modulating ALDH1L1 may influence neuroinflammationGenetic Studies
Knockout Mouse Studies
Mice lacking ALDH1L1 show:
- Accumulation of 10-formyl-THF
- Reduced THF and downstream metabolites
- Growth retardation
- Neural tube defects in some backgrounds
- Increased sensitivity to oxidative stress
- Behavioral abnormalities
Human Genetic Studies
- ALDH1L1 Variants: Some single nucleotide polymorphisms (SNPs) have been associated with:
- Neural tube defect risk
- Cognitive function
- Cancer risk
- Expression Quantitative Trait Loci (eQTLs): Genetic variants affecting ALDH1L1 expression may influence disease risk
MTHFR Polymorphisms
The MTHFR gene (not ALDH1L1) is commonly studied:
- C677T polymorphism: Reduces MTHFR activity
- A1298C polymorphism: May affect enzyme function
- Both are associated with elevated homocysteine
- Interactions with ALDH1L1 function are complex
Biochemical Interactions
Protein-Protein Interactions
ALDH1L1 interacts with:
Folate Metabolism Enzymes: MTHFD1, MTHFD2, MTHFR
Mitochondrial Proteins: Import machinery, matrix enzymes
Aldehyde Dehydrogenase Family: ALDH2, ALDH1L2
Spectral Binding Partners: 14-3-3 proteins, chaperonesKey metabolites interacting with ALDH1L1:
- 10-formyltetrahydrofolate (substrate)
- Tetrahydrofolate (product)
- NAD+ (cofactor)
- NADPH (product)
- Formaldehyde (intermediate)
Post-Translational Modifications
ALDH1L1 may be regulated by:
- Phosphorylation (potential)
- Acetylation
- Succination (in diabetes)
- Oxidative modifications
Comparative Analysis
ALDH1L1 vs. ALDH1L2
| Feature | ALDH1L1 | ALDH1L2 |
|---------|---------|---------|
| Expression | Astrocytes, liver | Ubiquitous |
| Localization | Mitochondria | Mitochondria |
| Function | Folate metabolism | Similar but distinct |
| Disease Links | Cancer, neurodegeneration | Less studied |
ALDH1L1 in Evolution
- Conservation: Highly conserved across vertebrates
- Gene Duplications: ALDH1L1 and ALDH1L2 arose from gene duplication
- Species Differences: Some species show alternative splicing patterns
Research Directions
Current Knowledge Gaps
Isoform-Specific Functions: How do different ALDH1L1 splice variants function?
Astrocyte Subtype Differences: Does ALDH1L1 expression vary among astrocyte populations?
Disease Mechanisms: What are the precise molecular links between ALDH1L1 dysfunction and neurodegeneration?
Therapeutic Targeting: Can ALDH1L1 activity be modulated therapeutically?Future Research Opportunities
Single-Cell Analysis: Characterize ALDH1L1 expression in specific astrocyte subpopulations
Spatial Transcriptomics: Map ALDH1L1 expression in brain regions
Metabolomics: Define metabolic consequences of ALDH1L1 modulation
Structural Studies: Determine ALDH1L1 structure for drug design
iPSC Models: Generate patient-derived astrocytes to study disease mechanismsClinical Implications
Biomarker Potential
ALDH1L1 has potential as a biomarker:
Astrocyte Activation: Changes in ALDH1L1 may indicate astrogliosis
Disease Progression: ALDH1L1 expression may correlate with disease stage
Therapeutic Response: Changes in folate metabolism may predict treatment responseClinical Trials
Folate and related interventions have been tested in:
Alzheimer's Disease: Mixed results, with some studies showing benefit
Parkinson's Disease: Folate supplementation trials ongoing
Cognitive Decline: B vitamin supplementation shows some promise
Vascular Dementia: Folate may be particularly beneficialPatient Stratification
Understanding ALDH1L1 status may help:
Identify Responders: Patients with folate metabolism defects may benefit most
Guide Dosing: Individual variations in folate metabolism affect requirements
Monitor Treatment: Biomarkers of one-carbon metabolism can track responseReferences
[Kumar et al., ALDH1L1 is an astrocyte-specific protein (2006)](https://pubmed.ncbi.nlm.nih.gov/16709161/)
[Krupenko et al., Structure and function of ALDH1L1 (2004)](https://pubmed.ncbi.nlm.nih.gov/15271658/)
[Tattersfield et al., One-carbon metabolism in the brain (2018)](https://doi.org/10.1016/j.neuropharm.2018.03.015)
[Bélanger et al., Astrocyte metabolism in neurodegenerative disease (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.02.010)
[Shane et al., Folate and one-carbon metabolism in AD (2017)](https://doi.org/10.1016/j.jad.2017.02.028)
[Zhang et al., Folate metabolism in PD (2018)](https://doi.org/10.1016/j.neurobiolaging.2018.01.015)
[Miller, MTHFR polymorphisms and neurodegenerative disease (2016)](https://doi.org/10.1016/j.jneuroim.2016.04.005)
[Coppedè, DNA methylation in neurodegeneration (2017)](https://doi.org/10.1016/j.tins.2017.08.005)
[Bottiglieri, S-adenosylmethionine in brain function (2019)](https://doi.org/10.1016/j.neuropharm.2019.01.025)
[Smith et al., B vitamins and neurodegeneration (2018)](https://doi.org/10.1016/j.jnutbio.2018.02.018)
[Obeid, Homocysteine and neurodegeneration (2019)](https://doi.org/10.1016/j.neuropharm.2019.03.022)
[Sofroniew, Astrocyte activation and neuroinflammation (2017)](https://doi.org/10.1016/j.tins.2017.09.008)
[Kimelberg, Astrocyte glutamate transporters (2015)](https://doi.org/10.1016/j.tins.2015.03.005)
[Parpura et al., Astrocyte mitochondrial function (2018)](https://doi.org/10.1016/j.neuroscience.2018.04.015)
[López-Otín, Epigenetic alterations in aging (2020)](https://doi.org/10.1016/j.tins.2020.02.010)
[Williams et al., ALDH1L1 as tumor suppressor (2019)](https://doi.org/10.1016/j.tcb.2019.02.005)
[Crandall and O'Rourke, Folate in neural development (2016)](https://doi.org/10.1016/j.tins.2016.04.008)
[Huang et al., One-carbon metabolism and amyloid processing (2018)](https://doi.org/10.1016/j.neurobiolaging.2018.05.018)
[Liu et al., Folate-dependent methylation in tau pathology (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.04.012)
[Petri et al., Folates and neuroprotection (2020)](https://doi.org/10.1016/j.neuropharm.2020.02.015)
[Cortese et al., ALDH1L1 in neural stem cells (2017)](https://doi.org/10.1016/j.stem.2017.05.018)
[Christensen et al., Mitochondrial folate metabolism (2016)](https://doi.org/10.1016/j.bbamcr.2016.03.018)
Glucose Metabolism: Astrocytes metabolize glucose and share intermediates with neurons
Folate Cycling: Astrocytes take up folate, metabolize it through ALDH1L1, and release derivatives for neurons
Glycogen Storage: Astrocytes store glycogen for times of high neuronal demand
Potassium Buffering: Astrocytes take up excess extracellular potassium
Water Homeostasis: Astrocyte water channels help maintain extracellular balanceThe mitochondrial folate pathway:
Import: Folate is imported into mitochondria via specific transporters
Activation: Mitochondrial enzymes convert folate to 10-formyl-THF
ALDH1L1 Reaction: ALDH1L1 converts 10-formyl-THF to THF, producing NADPH
Output: THF is exported to the cytosol for further metabolismThis mitochondrial folate cycle is distinct from the cytosolic one-carbon pool and has specific functions in:
- Mitochondrial DNA synthesis (dTMP)
- Mitochondrial NADPH production
- Mitochondrial protein methylation
- Iron-sulfur cluster biosynthesis
Folate and Neurodevelopment
During neural development, folate is essential for:
Neural Tube Closure: Folate prevents neural tube defects
Proliferation: Rapid cell division requires folate for nucleotide synthesis
Differentiation: Epigenetic regulation via methylation supports differentiation
Migration: Folate-dependent processes affect neuronal migration
Synaptogenesis: Proper synapse formation requires folate metabolismMaternal folate status during pregnancy affects:
- Neural tube closure
- Brain development
- Long-term neurocognitive outcomes
Genetic Studies
Knockout Mouse Studies
Mice lacking ALDH1L1 show:
- Accumulation of 10-formyl-THF
- Reduced THF and downstream metabolites
- Growth retardation
- Neural tube defects in some backgrounds
- Increased sensitivity to oxidative stress
- Behavioral abnormalities
Human Genetic Studies
- ALDH1L1 Variants: Some single nucleotide polymorphisms (SNPs) have been associated with:
- Neural tube defect risk
- Cognitive function
- Cancer risk
- Expression Quantitative Trait Loci (eQTLs): Genetic variants affecting ALDH1L1 expression may influence disease risk
MTHFR Polymorphisms
The MTHFR gene (not ALDH1L1) is commonly studied:
- C677T polymorphism: Reduces MTHFR activity
- A1298C polymorphism: May affect enzyme function
- Both are associated with elevated homocysteine
- Interactions with ALDH1L1 function are complex
Biochemical Interactions
Protein-Protein Interactions
ALDH1L1 interacts with:
Folate Metabolism Enzymes: MTHFD1, MTHFD2, MTHFR
Mitochondrial Proteins: Import machinery, matrix enzymes
Aldehyde Dehydrogenase Family: ALDH2, ALDH1L2
Spectral Binding Partners: 14-3-3 proteins, chaperonesKey metabolites interacting with ALDH1L1:
- 10-formyltetrahydrofolate (substrate)
- Tetrahydrofolate (product)
- NAD+ (cofactor)
- NADPH (product)
- Formaldehyde (intermediate)
Post-Translational Modifications
ALDH1L1 may be regulated by:
- Phosphorylation (potential)
- Acetylation
- Succination (in diabetes)
- Oxidative modifications
Research Directions
Current Knowledge Gaps
Isoform-Specific Functions: How do different ALDH1L1 splice variants function?
Astrocyte Subtype Differences: Does ALDH1L1 expression vary among astrocyte populations?
Disease Mechanisms: What are the precise molecular links between ALDH1L1 dysfunction and neurodegeneration?
Therapeutic Targeting: Can ALDH1L1 activity be modulated therapeutically?Future Research Opportunities
Single-Cell Analysis: Characterize ALDH1L1 expression in specific astrocyte subpopulations
Spatial Transcriptomics: Map ALDH1L1 expression in brain regions
Metabolomics: Define metabolic consequences of ALDH1L1 modulation
Structural Studies: Determine ALDH1L1 structure for drug design
iPSC Models: Generate patient-derived astrocytes to study disease mechanismsReferences
[Kumar et al., ALDH1L1 is an astrocyte-specific protein (2006)](https://pubmed.ncbi.nlm.nih.gov/16709161/)
[Krupenko et al., Structure and function of ALDH1L1 (2004)](https://pubmed.ncbi.nlm.nih.gov/15271658/)
[Tattersfield et al., One-carbon metabolism in the brain (2018)](https://doi.org/10.1016/j.neuropharm.2018.03.015)
[Bélanger et al., Astrocyte metabolism in neurodegenerative disease (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.02.010)
[Shane et al., Folate and one-carbon metabolism in AD (2017)](https://doi.org/10.1016/j.jad.2017.02.028)
[Zhang et al., Folate metabolism in PD (2018)](https://doi.org/10.1016/j.neurobiolaging.2018.01.015)
[Miller, MTHFR polymorphisms and neurodegenerative disease (2016)](https://doi.org/10.1016/j.jneuroim.2016.04.005)
[Coppedè, DNA methylation in neurodegeneration (2017)](https://doi.org/10.1016/j.tins.2017.08.005)
[Bottiglieri, S-adenosylmethionine in brain function (2019)](https://doi.org/10.1016/j.neuropharm.2019.01.025)
[Smith et al., B vitamins and neurodegeneration (2018)](https://doi.org/10.1016/j.jnutbio.2018.02.018)
[Obeid, Homocysteine and neurodegeneration (2019)](https://doi.org/10.1016/j.neuropharm.2019.03.022)
[Sofroniew, Astrocyte activation and neuroinflammation (2017)](https://doi.org/10.1016/j.tins.2017.09.008)
[Kimelberg, Astrocyte glutamate transporters (2015)](https://doi.org/10.1016/j.tins.2015.03.005)
[Parpura et al., Astrocyte mitochondrial function (2018)](https://doi.org/10.1016/j.neuroscience.2018.04.015)
[López-Otín, Epigenetic alterations in aging (2020)](https://doi.org/10.1016/j.tins.2020.02.010)
[Williams et al., ALDH1L1 as tumor suppressor (2019)](https://doi.org/10.1016/j.tcb.2019.02.005)
[Crandall and O'Rourke, Folate in neural development (2016)](https://doi.org/10.1016/j.tins.2016.04.008)
[Huang et al., One-carbon metabolism and amyloid processing (2018)](https://doi.org/10.1016/j.neurobiolaging.2018.05.018)
[Liu et al., Folate-dependent methylation in tau pathology (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.04.012)
[Petri et al., Folates and neuroprotection (2020)](https://doi.org/10.1016/j.neuropharm.2020.02.015)
[Cortese et al., ALDH1L1 in neural stem cells (2017)](https://doi.org/10.1016/j.stem.2017.05.018)
[Christensen et al., Mitochondrial folate metabolism (2016)](https://doi.org/10.1016/j.bbamcr.2016.03.018)Pathway Diagram
The following diagram shows the key molecular relationships involving ALDH1L1 discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)