Hypothesis Comparison

graph TD
    A["PDGFR-beta Selective Agonist"]
    B["PDGFR-beta Receptor Activation"]
    C["PLCgamma Pathway Activation"]
    D["IP3 and DAG Generation"]
    E["Calcium Mobilization"]
    F["Protein Kinase C Activation"]
    G["Myosin Light Chain Phosphorylation"]
    H["Pericyte Contractility Enhancement"]
    I["Blood-Brain Barrier Stabilization"]
    J["Glymphatic Flow Restoration"]
    K["Amyloid-beta Clearance"]
    L["Neuroinflammation Reduction"]
    M["Synaptic Protection"]
    N["Cognitive Function Improvement"]
    O["Neurodegeneration Progression Halt"]
    P["PI3K/Akt Pathway Inhibition"]

    A -->|"therapeutic intervention"| B
    B -->|"selective signaling"| C
    B -->|"alternative pathway"| P
    C -->|"phospholipase activation"| D
    D -->|"second messenger generation"| E
    D -->|"protein kinase activation"| F
    E -->|"intracellular Ca2+ increase"| G
    F -->|"contractile protein regulation"| G
    G -->|"smooth muscle contraction"| H
    H -->|"vascular tone restoration"| I
    H -->|"perivascular space regulation"| J
    I -->|"barrier function improvement"| K
    J -->|"interstitial fluid drainage"| K
    K -->|"protein aggregate removal"| L
    L -->|"neuroprotective environment"| M
    M -->|"neuronal preservation"| N
    N -->|"functional recovery"| O
    P -->|"proliferation inhibition"| H

    classDef mechanism fill:#4fc3f7
    classDef pathology fill:#ef5350
    classDef therapy fill:#81c784
    classDef outcome fill:#ffd54f
    classDef genetics fill:#ce93d8

    class A,B,C,D,E,F,G,P therapy
    class H,I,J mechanism
    class K,L,M outcome
    class N,O outcome

graph TD
    A["Orexin neurons in
lateral hypothalamus
circadian dysregulation"] -->|"reduced signaling"| B["OX1R and OX2R
orexin receptors
decreased activation"]
    
    B -->|"targeted modulation"| C["Orexin receptor
antagonist therapy
suvorexant/lemborexant"]
    
    C -->|"promotes"| D["Enhanced sleep
consolidation and
NREM sleep stages"]
    
    D -->|"activates"| E["Noradrenergic locus
coeruleus suppression
during sleep"]
    
    E -->|"reduces"| F["Astrocytic AQP4
water channel
polarization enhanced"]
    
    F -->|"facilitates"| G["CSF influx along
periarterial spaces
Virchow-Robin spaces"]
    
    G -->|"drives"| H["CSF-ISF mixing
in brain parenchyma
convective flow"]
    
    H -->|"mobilizes"| I["Amyloid-beta and
tau protein aggregates
from interstitium"]
    
    I -->|"clearance via"| J["Perivenous drainage
pathways activated
during sleep"]
    
    J -->|"exits to"| K["Cervical lymphatic
vessels and
systemic circulation"]
    
    A -->|"disrupts"| L["Circadian clock genes
Per1/Per2/Clock/Bmal1
expression altered"]
    
    L -->|"affects"| M["Glymphatic system
circadian regulation
10-20 fold variance"]
    
    M -->|"impairs"| N["Sleep-dependent
protein aggregate
clearance capacity"]
    
    N -->|"leads to"| O["Alzheimer pathology
progression and
neurodegeneration"]
    
    K -->|"reduces"| P["Brain toxic protein
burden and
oxidative stress"]
    
    P -->|"slows"| Q["Cognitive decline
and memory
impairment"]
    
    D -->|"strengthens"| R["Circadian rhythm
restoration and
sleep architecture"]
    
    R -->|"enhances"| M
    
    O -->|"without treatment"| S["Progressive
neuronal loss
and dementia"]

    classDef normal fill:#4fc3f7,stroke:#2196f3
    classDef therapeutic fill:#81c784,stroke:#4caf50
    classDef pathology fill:#ef5350,stroke:#f44336
    classDef outcome fill:#ffd54f,stroke:#ff9800
    classDef molecular fill:#ce93d8,stroke:#9c27b0

    class A,B,F,L,M pathology
    class C,D,E therapeutic
    class G,H,I,J,K,P,R normal
    class N,O,S pathology
    class Q,S outcome
    class A,B,F,I molecular