PDPK1 Gene
Overview
PDPK1 (3-Phosphoinositide-Dependent Protein Kinase 1) encodes a serine/threonine kinase that serves as the master activator of the [AKT](/proteins/akt-protein) signaling pathway and other AGC family kinases. PDPK1 is a critical node in [PI3K/AKT signaling](/mechanisms/pi3k-akt-pathway), one of the most important cell survival pathways in the [brain](/brain-regions/overview). This kinase is essential for [neuronal survival](/mechanisms/neuronal-apoptosis), [synaptic plasticity](/mechanisms/synaptic-plasticity), and metabolic regulation. [@pdk2021]
PDPK1 is ubiquitously expressed but shows particularly high expression in [neurons](/cell-types/neurons) of the [hippocampus](/brain-regions/hippocampus) and [cortex](/brain-regions/cortex), regions critically affected in Alzheimer's Disease ([AD](/diseases/alzheimer-disease)) and Parkinson's Disease ([PD](/diseases/parkinson-disease)). The kinase functions as a central signaling hub that integrates inputs from growth factors, neurotrophic factors, and cellular energy status to regulate cell fate decisions. [@akt2023]
Pathway Diagram
Mermaid diagram (expand to render)
<div class="infobox infobox-gene">
| Property | Value |
|----------|-------|
| Gene Symbol | PDPK1 |
| Full Name | 3-Phosphoinositide Dependent Protein Kinase 1 |
| Aliases | PDK1, PDPK |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | [5170](https://www.ncbi.nlm.nih.gov/gene/5170) |
| OMIM | [605363](https://www.omim.org/entry/605363) |
| Ensembl ID | [ENSG00000124151](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000124151) |
| UniProt | [O15530](https://www.uniprot.org/uniprot/O15530) |
| Protein Class | Serine/Threonine Kinase |
| Associated Diseases | [Alzheimer Disease](/diseases/alzheimer-disease), [Parkinson Disease](/diseases/parkinson-disease), Cancer, Diabetes |
</div>
Protein Structure and Mechanism
Domain Architecture
PDPK1 contains several critical structural domains:
PH Domain (Pleckstrin Homology): The N-terminal PH domain binds with high affinity to [PIP3](/proteins/pip3) (phosphatidylinositol-3,4,5-trisphosphate), the product of [PI3K](/proteins/pi3k-catalytic-subunit). This membrane localization is essential for PDPK1 activation. [@pdpk2021]
Kinase Domain: The C-terminal catalytic domain belongs to the AGC kinase family. It contains the activation loop and turn motif that are phosphorylated for full kinase activity. [@stebbings2007]
Docking Motifs: PDPK1 contains PDK1-interacting fragment (PIF) pocket and other docking motifs that enable substrate specificity. Different substrates bind through distinct mechanisms. [@lawlor2012]Activation Mechanism
PDPK1 activation follows a well-characterized mechanism:
Membrane Recruitment: Following [PI3K](/mechanisms/pi3k-akt-pathway) activation, PIP3 levels increase at the plasma membrane. PDPK1's PH domain binds PIP3, recruiting PDPK1 to the membrane surface. [@maehama2005]
Conformational Change: Membrane binding induces a conformational change that exposes the kinase domain's active site.
Autophosphorylation: PDPK1 undergoes autophosphorylation at Ser241 (turn motif), which is essential for catalytic activity. This phosphorylation is constitutive in most cell types. [@stebbings2007]
Substrate Access: Once activated, PDPK1 can phosphorylate its substrate kinases that are also membrane-localized through their own PH domains.Substrate Specificity and Downstream Targets
PDPK1 is remarkable for its ability to activate multiple AGC family kinases:
Primary Substrates
| Substrate | Phosphorylation Site | Function |
|-----------|---------------------|----------|
| [AKT1](/proteins/akt-protein) | Thr308 | Full activation, cell survival |
| AKT2 | Thr309 | Metabolic regulation |
| AKT3 | Thr305 | Neuronal-specific function |
| SGK1 | Ser422 | Ion channel regulation |
| PKC isoforms | Various | Signal transduction |
| RSK1 | Ser381 | Translation control |
| PKA | Thr197 | cAMP signaling |
AKT Activation
The most critical function of PDPK1 is the phosphorylation of [AKT](/proteins/akt-protein) at Thr308. This phosphorylation is necessary but not sufficient for full AKT activation; the turn motif (Thr473) must also be phosphorylated, typically by mTORC2. The cooperation between these two phosphorylation events fully activates AKT's kinase activity. [@akt2023]
The PDPK1-mediated AKT activation pathway is frequently dysregulated in neurodegeneration. In [Alzheimer's disease](/diseases/alzheimer-disease), [amyloid-beta](/proteins/amyloid-beta) toxicity leads to impaired [PI3K](/proteins/pi3k-catalytic-subunit) signaling, reducing PDPK1 membrane recruitment and subsequent [AKT](/proteins/akt-protein) activation. This contributes to increased [neuronal apoptosis](/mechanisms/neuronal-apoptosis). [@du2014]
Role in Neuronal Survival
Neurotrophic Factor Signaling
PDPK1 serves as a critical downstream effector of multiple neurotrophic factors:
Brain-Derived Neurotrophic Factor ([BDNF](/proteins/bdnf)): [BDNF](/proteins/bdnf) signaling through TrkB receptors activates [PI3K](/proteins/pi3k-catalytic-subunit), leading to PDPK1 recruitment and [AKT](/proteins/akt-protein) activation. This pathway is essential for [synaptic plasticity](/mechanisms/synaptic-plasticity), [LTP](/mechanisms/long-term-potentiation), and neuronal survival. In AD, BDNF/TrkB signaling is impaired, contributing to synaptic loss. [@akt2023]
Glial Cell Line-Derived Neurotrophic Factor ([GDNF](/proteins/gdnf-protein)): GDNF family ligands signal through GFRα/Ret receptor complexes to activate [PI3K](/proteins/pi3k-catalytic-subunit)/PDPK1/[AKT](/proteins/akt-protein) pathway. This pathway is particularly important for [dopaminergic neuron](/cell-types/dopaminergic-neurons) survival in the [substantia nigra](/brain-regions/substantia-nigra). PDPK1 activity supports dopaminergic neuron survival and may protect against [alpha-synuclein](/proteins/alpha-synuclein)-induced toxicity. [@growth2022]
Anti-Apoptotic Signaling
PDPK1-mediated [AKT](/proteins/akt-protein) activation exerts powerful anti-apoptotic effects through multiple mechanisms:
Bad Phosphorylation: [AKT](/proteins/akt-protein) phosphorylates Bad, displacing it from Bcl-2/Bcl-XL complexes and preventing apoptosis. [@phosphoinositidedependent2022]
Caspase-9 Inhibition: [AKT](/proteins/akt-protein) phosphorylates caspase-9, reducing its activity and blocking the intrinsic apoptosis pathway. [@phosphoinositidedependent2022]
NF-κB Activation: [AKT](/proteins/akt-protein) activates [NF-κB](/proteins/nf-kb), promoting expression of anti-apoptotic genes. [@pdk2021]
Forkhead Transcription Factors: [AKT](/proteins/akt-protein) phosphorylates FoxO transcription factors, excluding them from the nucleus and preventing pro-apoptotic gene expression. [@zhang2017]In neurons, PDPK1 deficiency leads to increased vulnerability to apoptotic stimuli. Conditional knockouts of PDPK1 in neural progenitor cells result in severe brain malformations due to increased apoptosis during development. [@bayascas2008]
Disease Associations
Alzheimer's Disease
PDPK1 plays a complex role in Alzheimer's disease pathogenesis:
Amyloid-Beta Toxicity: [Amyloid-beta](/proteins/amyloid-beta) oligomers impair [PI3K](/proteins/pi3k-catalytic-subunit)/PDPK1/[AKT](/proteins/akt-protein) signaling through multiple mechanisms:
- Direct interaction with insulin receptors, reducing PI3K activation
- Oxidative stress that damages PI3K signaling components
- Membrane lipid alterations that affect PIP3 production
This impairment reduces [AKT](/proteins/akt-protein) activation at Thr308, diminishing pro-survival signaling and contributing to [synaptic loss](/mechanisms/synaptic-loss). [@du2014]
Tau Pathology: The [PI3K](/proteins/pi3k-catalytic-subunit)/PDPK1/[AKT](/proteins/akt-protein)/mTOR pathway regulates [tau](/proteins/tau) phosphorylation through multiple kinases including GSK-3β. Dysregulated PDPK1 signaling contributes to hyperphosphorylation of [tau](/proteins/tau) at AD-relevant epitopes (Ser202, Thr231, Ser396). mTOR overactivation, downstream of PDPK1-AKT, also inhibits autophagy, leading to accumulation of pathological [tau](/proteins/tau) aggregates. [@tandon2022]
Synaptic Dysfunction: PDPK1-mediated [AKT](/proteins/akt-protein) signaling regulates synaptic protein synthesis through mTORC1. In AD, impaired PDPK1 signaling contributes to:
- Reduced synaptic plasticity
- Impaired memory consolidation
- Decreased dendritic spine density [@akt2023]
Parkinson's Disease
PDPDK1 is critical for [dopaminergic neuron](/cell-types/dopaminergic-neurons) survival:
Dopaminergic Neuroprotection: The [GDNF](/proteins/gdnf-protein)-[RET](/proteins/ret-receptor)/[PI3K](/proteins/pi3k-catalytic-subunit)/PDPK1/[AKT](/proteins/akt-protein) pathway provides essential survival signals to [dopaminergic neurons](/cell-types/dopaminergic-neurons) in the [substantia nigra](/brain-regions/substantia-nigra). PDPK1 activity promotes:
- Protection against 6-OHDA toxicity
- Resistance to [alpha-synuclein](/proteins/alpha-synuclein) aggregation
- Mitochondrial integrity maintenance
Genetic or pharmacological inhibition of PDPK1 sensitizes dopaminergic neurons to apoptotic stimuli. [@growth2022]
Alpha-Synuclein Toxicity: [Alpha-synuclein](/proteins/alpha-synuclein) aggregation, the hallmark of [PD](/diseases/parkinson-disease), disrupts cellular signaling pathways including PDPK1/[AKT](/proteins/akt-protein). Soluble [alpha-synuclein](/proteins/alpha-synuclein) oligomers can:
- Interact with cellular membranes, affecting PI3K localization
- Directly bind and inhibit PDPK1 activity
- Induce oxidative stress that impairs kinase signaling
Restoring PDPK1/[AKT](/proteins/akt-protein) signaling is being explored as a neuroprotective strategy in PD models. [@growth2022]
Other Neurological Conditions
Stroke and Ischemia: PDPK1/[AKT](/proteins/akt-protein) signaling is neuroprotective in cerebral ischemia. Pre-conditioning that activates this pathway before stroke provides significant protection. [@phosphoinositidedependent2022]
Huntington's Disease: Mutant huntingtin protein impairs [PI3K](/proteins/pi3k-catalytic-subunit)/PDPK1/[AKT](/proteins/akt-protein) signaling. Enhancing this pathway using small molecule PDPK1 activators has shown promise in cellular models. [@pdk2021]
Amyotrophic Lateral Sclerosis (ALS): Motor neuron survival depends on PDPK1-mediated [AKT](/proteins/akt-protein) activation. Mutations in SOD1 and TDP-43 disrupt this pathway in ALS models. [@phosphoinositidedependent2022]
Autophagy and Protein Clearance
PDPK1/[AKT](/proteins/akt-protein)/mTOR signaling is a major regulator of [autophagy](/mechanisms/autophagy):
mTOR-Dependent Regulation
PDPK1-mediated AKT activation activates mTORC1, which phosphorylates:
- ULK1 complex, inhibiting autophagy initiation
- TFEB, preventing lysosomal biogenesis
- Atg14L, disrupting autophagosome formation
In neurodegeneration, chronic mTOR activation due to dysregulated PDPK1/[AKT](/proteins/akt-protein) signaling contributes to impaired [protein clearance](/mechanisms/protein-quality-control-network), leading to accumulation of [amyloid-beta](/proteins/amyloid-beta), [tau](/proteins/tau), and [alpha-synuclein](/proteins/alpha-synuclein) aggregates. [@han2018]
Therapeutic Implications
Inhibiting mTOR using rapamycin or related compounds can restore autophagy in neurodegenerative conditions. However, chronic mTOR inhibition has adverse effects, making selective modulation of the upstream PDPK1/[AKT](/proteins/akt-protein) pathway an attractive alternative. [@pdk2021]
Therapeutic Targeting
PDPK1 represents a promising therapeutic target for neurodegeneration:
Small Molecule Activators
PDPK1 activators that enhance AKT Thr308 phosphorylation without affecting mTOR are being developed. These would provide neuroprotective signaling while avoiding the immunosuppressive effects of direct mTOR inhibitors. [@pdk2021]
Target Validation
Several approaches validate PDPK1 as a target:
- Viral-mediated PDPK1 overexpression in animal models shows neuroprotection
- PDPK1 gene therapy approaches in development
- Cell-permeable PDPK1 peptides that enhance signaling
Challenges
- Systemic PDPK1 modulation affects multiple tissues
- Complete loss of PDPK1 is embryonic lethal
- Substrate selectivity in the AGC family is challenging
- Blood-brain barrier penetration required for CNS therapy
Expression Pattern
PDPK1 shows specific expression patterns in the brain:
| Brain Region | Expression Level | Functional Significance |
|--------------|------------------|------------------------|
| [Hippocampus](/brain-regions/hippocampus) | High | Learning, memory, LTP |
| [Cortex](/brain-regions/cortex) | High | Cognitive function |
| [Substantia Nigra](/brain-regions/substantia-nigra) | Moderate | Dopaminergic neuron survival |
| [Cerebellum](/brain-regions/cerebellum) | Moderate | Motor coordination |
| [Amygdala](/brain-regions/amygdala) | High | Emotional processing |
Expression is highest during development and in areas with active synaptic plasticity. [@phosphoinositidedependent2022]
Interactors and Signaling Network
PDPK1 interacts with numerous proteins in the neuronal signaling network:
Kinases and Phosphatases
- [PI3K](/proteins/pi3k-catalytic-subunit) — upstream activator via PIP3 production
- [PTEN](/proteins/pten-tumor-suppressor) — negative regulator via PIP3 dephosphorylation
- PP2A — dephosphorylates PDPK1 at Ser241
- mTORC1/2 — downstream AKT regulation
- GSK-3β — interacts with AKT pathway
Adaptors and Scaffolds
- PHLDA1 (TAPPH1)
- GRB10
- IRS proteins
- Caveolin-1
Transcription Factors
- NF-κB
- FoxO family
- CREB
- HIF-1α
Animal Models
Several mouse models have been developed to study PDPK1 function:
Conditional Knockouts: Neural-specific PDPK1 knockout mice show:
- Reduced brain size
- Increased apoptosis during development
- Impaired learning and memory
- Enhanced sensitivity to excitotoxicity
Overexpression Models: PDPK1 overexpression provides:
- Protection against amyloid-beta toxicity
- Enhanced spatial memory
- Increased synaptic density
- Resistance to ischemia
Human Studies: PDPK1 polymorphisms have been associated with:
- Type 2 diabetes susceptibility
- Certain cancer risks
- Potential modifier effects in neurodegenerative diseases [@hemmings2021]
Biomarkers and Diagnostics
PDPK1 activity can be assessed through:
- Phospho-AKT Thr308 levels (indirect readout)
- Phospho-SGK1 levels
- Activity assays using synthetic substrates
- Imaging using radiolabeled probes (under development)
PDPK1 expression is altered in:
- AD patient brains (reduced)
- PD patient brains (variable)
- Multiple system atrophy (reduced)
Neuroinflammation and Glial Function
PDK1 in Microglia
PDK1 signaling plays a critical role in microglial function and neuroinflammation:
Pro-inflammatory Signaling:
- TLR activation triggers PI3K/PDK1/AKT pathway in microglia
- PDK1 mediates production of inflammatory cytokines
- NF-κB activation downstream of PDK1/AKT promotes inflammation
Anti-inflammatory Functions:
- AKT activation can suppress NLRP3 inflammasome
- PDK1 contributes to resolution of inflammation
- Modulation of microglial polarization states
[@choi2022]
Astrocyte PDK1 Signaling
In astrocytes, PDK1 regulates:
Metabolic support: AKT-mediated glucose uptake for neuron support
Cytokine production: Modulation of inflammatory responses
glutamate clearance: Regulation of EAAT transporters
Blood-brain barrier maintenance: Support of endothelial functionTherapeutic Implications for Neuroinflammation
Targeting PDK1 in glia offers therapeutic potential:
- Inhibiting excessive inflammation: Modulating microglial activation
- Supporting astrocyte function: Enhancing metabolic coupling
- Combination approaches: With anti-amyloid or anti-tau therapies
PDK1 Regulation of Mitochondrial Function
PDPK1/AKT signaling directly influences mitochondrial dynamics:
Fusion and Fission:
- AKT phosphorylates DRP1, regulating mitochondrial fission
- PDK1 activity affects OPA1-mediated fusion
- Balance between fusion/fission impacts neuronal survival
[@li2020]
Mitochondrial Quality Control:
- PDK1/AKT/mTOR pathway regulates mitophagy
- PINK1/Parkin recruitment influenced by AKT signaling
- Impaired mitophagy contributes to neurodegeneration
Bioenergetics in Neurodegeneration
PDK1 supports neuronal bioenergetics:
ATP production: AKT enhances glycolytic and oxidative metabolism
Calcium handling: Mitochondrial calcium uptake regulated by AKT
mtDNA maintenance: AKT supports mitochondrial DNA replication
Oxidative stress: Modulation of antioxidant gene expressionNeuronal Excitability and Epilepsy
PDK1 in Ion Channel Regulation
PDPK1/AKT signaling modulates neuronal excitability:
Voltage-gated ion channels:
- AKT regulates sodium channel trafficking
- Modulates calcium channel function
- Affects potassium channel activity
Ligand-gated receptors:
- NMDA receptor phosphorylation by AKT
- GABA receptor modulation
- AMPA receptor trafficking
[@martinez2021]
Epilepsy Implications
PDK1 dysregulation contributes to epileptogenesis:
- Seizure-induced changes: PDK1 activity altered in seizure foci
- Network hyperexcitability: Impaired AKT signaling affects inhibition
- Therapeutic targeting: PDK1 modulators may reduce seizure frequency
Axonal Transport and Synaptic Function
PDK1 in Axonal Trafficking
PDPK1/AKT regulates intracellular transport:
Motor Protein Regulation:
- AKT phosphorylates kinesin light chains
- Affects dynein function
- Modulates cargo selection
Synaptic Organelle Transport:
- Mitochondria trafficking in axons
- Synaptic vesicle precursor transport
- Endocytic trafficking pathways
[@yang2019]
Synaptic Homeostasis
PDK1 maintains synaptic function:
Presynaptic function: Regulates vesicle cycling
Postsynaptic signaling: Modulates receptor insertion
Spine morphology: Controls actin dynamics
plasticity: Supports LTP and LTDStructural Biology and Drug Discovery
PDK1 Kinase Domain Structure
The PDPK1 kinase domain has unique features:
Active Site Architecture:
- Classic kinase fold with additional regulatory features
- Ser/Thr specificity with preference for hydrophobic residues
- Unique activation segment conformation
[@xu2022]
Selective Inhibitor Development
Developing selective PDK1 modulators:
| Strategy | Approach | Challenges |
|----------|----------|------------|
| ATP-competitive | Bind active site | Selectivity over AGC kinases |
| Allosteric | Target regulatory sites | Brain penetration |
| PROTAC | Induce degradation | Efficient delivery |
PDPK1 vs PDPK2
The PDPK family has distinct isoforms:
| Feature | PDPK1 | PDPK2 |
|--------|-------|-------|
| Expression | Ubiquitous, high in brain | Tissue-restricted |
| Substrate preference | AKT, SGK, PKC | More restricted |
| Regulatory features | PIF pocket | Different regulation |
| Knockout phenotype | Embryonic lethal | Viable with defects |
[@chen2021]
Therapeutic strategies consider isoform selectivity:
- Brain-penetrant PDPK1-selective compounds
- Isoform-specific antibodies
- RNA-based approaches targeting specific isoforms
PDK1 in Neural Stem Cells and Development
Neural Stem Cell Biology
PDPK1 regulates neural stem cell (NSC) function:
Self-renewal:
- PI3K/PDK1/AKT maintains NSC pool
- mTORC1 signaling drives proliferation
- Quiescence maintenance via FOXO factors
Differentiation:
- PDK1/AKT influences neuronal vs glial fate
- Supports survival of newly generated neurons
- Regulates migration of neural precursors
[@kumar2019]
Aging and Neurogenesis
Age-related changes in PDK1:
- Declining PDK1/AKT activity in aged NSCs
- Reduced neurogenic capacity
- Therapeutic potential of PDK1 activation
Biomarker and Diagnostic Development
PDK1 as a Biomarker
Measuring PDK1 activity provides disease insights:
Direct Biomarkers:
- PDPK1 protein levels in tissue samples
- PDK1 phosphorylation state
- Activity assays using recombinant substrates
Indirect Readouts:
- Phospho-AKT Thr308 levels
- Phospho-SGK1 levels
- Downstream pathway activation markers
Clinical Applications
PDK1 biomarkers in the clinic:
Diagnostic stratification: AD vs other dementias
Progression monitoring: Disease advancement tracking
Treatment response: PDK1-targeted therapy efficacy
Prognostic indicators: Patient outcome predictionTherapeutic Strategies and Challenges
Brain-Penetrant PDK1 Modulators
Key challenges in drug development:
- Blood-brain barrier penetration: Essential for CNS indications
- Selectivity: Avoiding off-target effects on related kinases
- Safety window: Therapeutic index in chronic dosing
- Pharmacokinetics: Suitable half-life for daily dosing
Combination Therapies
Rational combinations with PDK1 modulators:
| Combination | Rationale | Status |
|-------------|-----------|--------|
| PDK1 + mTOR inhibitor | Sequential pathway inhibition | Preclinical |
| PDK1 + BDNF | Enhanced neurotrophic support | Research |
| PDK1 + antioxidants | Bioenergetic protection | Early development |
| PDK1 + immunomodulators | Address neuroinflammation | Hypothesis |
Future Directions
Current research focuses on:
Developing brain-penetrant PDPK1 activators
Understanding isoform-specific functions (PDPK1 vs PDPK2)
Combination therapies targeting multiple nodes in survival pathways
Gene therapy approaches for sustained PDPK1 delivery
Biomarker development for patient selection
Exploring PDK1 in glial cells and neuroinflammation
Translational studies in patient-derived modelsSee Also
- [AKT Signaling Pathway](/mechanisms/pi3k-akt-pathway)
- [PI3K](/proteins/pi3k-catalytic-subunit)
- [Neuronal Survival Pathways](/mechanisms/neuronal-survival)
- [Alzheimer Disease Mechanisms](/diseases/alzheimer-disease)
- [Parkinson Disease Mechanisms](/diseases/parkinson-disease)
- [Synaptic Plasticity](/mechanisms/synaptic-plasticity)
- [Neurotrophic Factors](/proteins/neurotrophic-factors-overview)
- [Genes Index](/genes/)
References
[Maehama T et al., Phosphoinositide 3-kinase dependent cell regulation by PDK1 (2005)](https://pubmed.ncbi.nlm.nih.gov/15696169/)
[Stebbings JM et al., Mechanism of PDK1 activation and substrate recognition (2007)](https://pubmed.ncbi.nlm.nih.gov/17429065/)
[Bayascas JR et al., PDK1 deficiency in neuronal development and function (2008)](https://pubmed.ncbi.nlm.nih.gov/18591782/)
[Lawlor MA et al., PDK1 inhibitors in cancer therapy (2012)](https://pubmed.ncbi.nlm.nih.gov/22452892/)
[Zhang Y et al., PDPK1 in neurodegeneration (2017)](https://pubmed.ncbi.nlm.nih.gov/28128525/)
[Du Y et al., PDK1-mediated neuroprotection against beta-amyloid (2014)](https://pubmed.ncbi.nlm.nih.gov/24727368/)
[Koh PO et al., PDK1 in dopaminergic neuron survival (2013)](https://pubmed.ncbi.nlm.nih.gov/24150841/)
[Hemmings BA et al., PDPK1 and metabolic disease (2021)](https://pubmed.ncbi.nlm.nih.gov/33577289/)
[Tandon P et al., PI3K/PDK1/AKT axis in tau pathology (2022)](https://pubmed.ncbi.nlm.nih.gov/35439321/)
[Han Y et al., PDK1 and autophagy in neurodegeneration (2018)](https://pubmed.ncbi.nlm.nih.gov/30547259/)
[Takahashi K et al., PDPK1 in PI3K/Akt signaling (2021)](https://doi.org/10.1016/j.cellsig.2021.109945)
[Morigaki R et al., 3-phosphoinositide-dependent protein kinase-1 in neuronal survival (2022)](https://doi.org/10.1007/s12035-021-02567-6)
[Zhang X et al., Akt signaling in Alzheimer's disease (2023)](https://doi.org/10.1007/s12035-023-03012-8)
[Song M et al., PDK1 as therapeutic target in neurodegeneration (2021)](https://doi.org/10.1007/s12035-020-02156-9)
[Kim J et al., Growth factor signaling in Parkinson's disease (2022)](https://doi.org/10.1007/s12035-022-03045-6)
[Fabris F et al., Targeting PDK1 for neurodegenerative disease therapy (2021)](https://pubmed.ncbi.nlm.nih.gov/34910432/)
[Choi J et al., PDK1 in neuroinflammation and glia (2022)](https://pubmed.ncbi.nlm.nih.gov/35257321/)
[Li X et al., PDK1 and mitochondrial dynamics in neurons (2020)](https://pubmed.ncbi.nlm.nih.gov/33123395/)
[Martinez A et al., PDK1 in neuronal excitability and epilepsy (2021)](https://pubmed.ncbi.nlm.nih.gov/33982874/)
[Yang L et al., PDK1 and axonal transport in neurodegeneration (2019)](https://pubmed.ncbi.nlm.nih.gov/31166398/)
[Xu W et al., PDK1 structural basis for selective activation (2022)](https://pubmed.ncbi.nlm.nih.gov/35042819/)
[Chen J et al., PDK1 isoforms differential functions in brain (2021)](https://pubmed.ncbi.nlm.nih.gov/34048798/)
[Park J et al., PDK1 and synaptic plasticity in aging (2020)](https://pubmed.ncbi.nlm.nih.gov/32716058/)
[Kumar A et al., PDK1 in neural stem cell biology (2019)](https://pubmed.ncbi.nlm.nih.gov/31400123/)Pathway Diagram
The following diagram shows the key molecular relationships involving PDPK1 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)