Table 1:
Therapeutic targets for AD based on molecular signaling pathways
| Sr. No. | Molecular Signaling Pathways | Therapeutic targets | References |
|---|---|---|---|
| 1 | Amyloid cascade signaling | Aβ, APP, BACE1, PSEN1, PSEN2, ApoE | 480 |
| 2 | Tau and Neurofibrillary tangles | Tau protein, kinases | 29 |
| 3 | Genetic mutation | APP, PSEN1, PSEN2, ApoE4 | 2 |
| 4 | Neurotransmitter signaling | NMDA receptor, acetyl-cholinesterase (AchE), Glutamatergic and GABAergic receptors | 162,181 |
| 5 | Mitochondrial dysfunction | Mitochondrial respiratory enzymes, mitochondrial ROS | 201,202 |
| 6 | Endoplasmic reticulum stress | Unfolded Protein Response (UPR), Stress sensors (IREI, PERK, and ATFE6) | 481 |
| 7 | Oxidative stress | Reactive oxygen species (ROS), Mitochondrial dysfunction, Advanced glycation end products (AGEs) | 224,226 |
| 8 | Neuroinflammatory signaling | Proinflammatory elements such as chemokines, IL-2β, IL-6, IL-12, INF-γ, TNF-α, NO, ROS, IL-1β | 39,40,251 |
| 9 | Ubiquitin-Proteasomal System | Ubiquitin activating enzyme (E1), Ubiquitin conjugating enzyme (E2), UCHL1, 26 S Proteasome | 42 |
| 10 | Autophagy/Endosomal-lysosomal system | Mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), PSEN1, SNCA, UBQLN1, UCHL1 ATG7, CDK5, CLU, CTSDITPR1, MAPT, BCL2, BECN1, FOXO1, and GFAP | 282,291,294,434 |
| 11 | Protein misfolding and molecular chaperones | Heat Shock Proteins (HSPs), HSP60 and HSP70 | 296 |
| 12 | Insulin Signaling | Insulin Receptors (IRs), Insulin degrading Enzymes (IDE), Akt, GSK-3β | 305 |
| 13 | Lipid/Cholesterol metabolism | ApoE, HMG-CoA reductase, Acyl CoA-Cholesterol O-acyl transferases (ACAT) | 52,74,482 |
| 14 | Calcium (Ca2+) signaling | Ca2+ homeostasis | 365 |
| 15 | Excitotoxicity | Glutamate, N-methyl-D-aspartate (NMDA) receptors, | 59 |
| 16 | Neurotrophic factors signaling | Brain-Derived Neurotrophic Factor (BDNF), Nerve Growth Factor (NGF), Neurotrophin-3 (NT-3), Neurotrophin-4/5, Trk receptors (TrkA, TrkB, TrkC) | 51 |
| 17 | Wnt/β-catenin signaling | β-catenin, GSK-3β | 391 |
| 18 | Leptin signaling | Leptin, Leptin receptor (ObR) | 58,399 |
| 19 | Blood-Brain Barrier (BBB) dysfunction | Receptor for advanced glycation end products (RAGE), Low-density lipoprotein receptor-related protein 1 (LRP-1) | 419 |
| 20 | Gut Microbiota and Nutrients | Diet and Nutritional interventions (prebiotics and probiotics), Gut microbes | 61 |