Maintain Your Brain – Appendix A

No single drug is optimal to keep the brain on the healthy pathway . . . Why?

Such a drug would have to do all of the following:

    1. Reduce APPβ-cleavage
    2. Reduce γ-cleavage
    3. Increase α-cleavage
    4. Reduce caspase-6 cleavage
    5. Reduce caspase-3 cleavage
    6. Prevent amyloid-beta oligomerization
    7. Increase neprilysin
    8. Increase IDE (insulin-degrading enzyme)
    9. Increase microglial clearance of Aβ
    10. Increase autophagy
    11. Increase BDNF (brain-derived neurotrophic factor)
    12. Increase NGF (nerve growth factor)
    13. Increase netrin-1
    14. Increase ADNP (activity-dependent neuroprotective protein)
    15. Increase VIP (vasoactive intestinal peptide)
    16. Reduce homocysteine
    17. Increase PP2A (protein phosphatase 2A) activity
    18. Reduce phospho-tau Increase phagocytosis index
    19. Increase insulin sensitivity
    20. Enhance leptin sensitivity
    21. Improve axoplasmic transport
    22. Enhance mitochondrial function and biogenesis
    23. Reduce oxidative damage and optimize ROS (reactive oxygen species) production Enhance cholinergic neurotransmission
    24. Increase synaptoblastic signaling
    25. Reduce synaptoclastic signaling
    26. Improve LTP (long-term potentiation)
    27. Optimize estradiol
    28. Optimize progesterone
    29. Optimize E2: P (estradiol to progesterone) ratio
    30. Optimize free T3
    31. Optimize free T4
    32. Optimize TSH (thyroid-stimulating hormone)
    33. Optimize pregnenolone
    34. Optimize testosterone
    35. Optimize cortisol
    36. Optimize DHEA (dehydroepiandrosterone)
    37. Optimize insulin secretion and signaling
    38. Activate PPAR-γ (peroxisome proliferator-activated receptor gamma)
    39. Reduce inflammation
    40. Increase resolvins
    41. Enhance detoxification
    42. Improve vascularization
    43. Increase cAMP (cyclic adenosine monophosphate)
    44. Increase glutathione
    45. Provide synaptic components
    46. Optimize all metals I
    47. ncrease GABA (gamma-aminobutyric acid)
    48. Increase vitamin D signaling Increase SirT1 (silent information regulator T1)
    49. Reduce NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells)
    50. Increase telomere length
    51. Reduce glial scarring
    52. Enhance stem-cell-mediated brain repair

And even this list may not be exhaustive. As you can see, this is a very tall order for a single drug.

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