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. 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.