f Cannabis and Cannabidiol: Pioneering Treatment for the Nervous System with Alzheimer's Disease and Peripheral Organ Involvement with Nonalcoholic Fatty Liver Disease (NAFLD)

References

1. BattistaN. FezzaF. MaccarroneM. Endocannabinoids and their involvement in the neurovascular system.Curr. Neurovasc. Res.20041212914010.2174/1567202043480107 16185189
   [Google Scholar]
2. De CaroC. LeoA. CitraroR. The potential role of cannabinoids in epilepsy treatment.Expert Rev. Neurother.201717111069107910.1080/14737175.2017.1373019 28845714
   [Google Scholar]
3. EspositoG. De FilippisD. CarnuccioR. IzzoA.A. IuvoneT. The marijuana component cannabidiol inhibits β-amyloid-induced tau protein hyperphosphorylation through Wnt/β-catenin pathway rescue in PC12 cells.J. Mol. Med. (Berl.)200684325325810.1007/s00109‑005‑0025‑1 16389547
   [Google Scholar]
4. EspositoG. De FilippisD. MaiuriM.C. De StefanoD. CarnuccioR. IuvoneT. Cannabidiol inhibits inducible nitric oxide synthase protein expression and nitric oxide production in β-amyloid stimulated PC12 neurons through p38 MAP kinase and NF-κB involvement.Neurosci. Lett.20063991-2919510.1016/j.neulet.2006.01.047 16490313
   [Google Scholar]
5. KalkmanH.O. The role of the phosphatidylinositide 3-kinase–protein kinase B pathway in schizophrenia.Pharmacol. Ther.2006110111713410.1016/j.pharmthera.2005.10.014 16434104
   [Google Scholar]
6. LanphierC.M. McCauleyL.G.F. Prevalence and consequences of nonmedical use of drugs among Canadian Forces personnel: 1982.Am. J. Drug Alcohol Abuse1985113-423124710.3109/00952998509016864 4091160
   [Google Scholar]
7. ChenS. KimJ.K. The role of cannabidiol in liver disease: A systemic review.Int. J. Mol. Sci.2024254237010.3390/ijms25042370 38397045
   [Google Scholar]
8. MaieseK. Cardiovascular and nonalcoholic fatty liver disease: Sharing common ground through SIRT1 pathways.World J. Cardiol.2024161163264310.4330/wjc.v16.i11.632 39600987
   [Google Scholar]
9. Abo El-MagdN.F. El-KashefD.H. El-SherbinyM. ErakyS.M. Hepatoprotective and cognitive-enhancing effects of hesperidin against thioacetamide-induced hepatic encephalopathy in rats.Life Sci.202331312128010.1016/j.lfs.2022.121280 36526046
   [Google Scholar]
10. GonzálezD. CamposG. PütterL. Role of WISP1 in stellate cell migration and liver fibrosis.Cells20241319162910.3390/cells13191629 39404393
    [Google Scholar]
11. SchiavoniL.C. BaptistaV.I.A. QuintanaH.T. LazzarinM.C. de OliveiraF. Protective effects of insulin treatment in the morphological alterations and oxidative damage to DNA in the liver of young rats subjected to skin scald burn injury.Int. J. Burns Trauma202515311512410.62347/ANQA2365 40688052
    [Google Scholar]
12. ShoffS. ThomasS. JiP. ParentiM. SlupskyC.M. Dual impact of iron deficiency and antibiotics on host metabolism: A tissue-level analysis.Metabolites202515854910.3390/metabo15080549 40863165
    [Google Scholar]
13. SunW.D. ZhuX.J. LiJ.J. MeiY.Z. LiW.S. LiJ.H. Nicotinamide N-methyltransferase (NNMT): A novel therapeutic target for metabolic syndrome.Front. Pharmacol.202415141047910.3389/fphar.2024.1410479 38919254
    [Google Scholar]
14. ZhangZ. WuG. YangJ. Integrated network pharmacology, transcriptomics and metabolomics to explore the material basis and mechanism of Danggui-Baishao herb pair for treating hepatic fibrosis.J. Ethnopharmacol.2025337Pt 111883410.1016/j.jep.2024.118834 39299362
    [Google Scholar]
15. VrechiT.A.M. GuaracheG.C. OliveiraR.B. Cannabidiol-induced autophagy ameliorates tau protein clearance.Neurotox. Res.2025431810.1007/s12640‑025‑00729‑3 39900844
    [Google Scholar]
16. Colín-MartínezE. Espino-de-la-FuenteC. AriasC. Age- and sex-associated wnt signaling dysregulation is exacerbated from the early stages of neuropathology in an alzheimer’s disease model.Neurochem. Res.202449113094310410.1007/s11064‑024‑04224‑7 39167347
    [Google Scholar]
17. EbrahimifarA. AhmadiS. RostamzadehJ. RahimiK. Vanadyl sulfate restores memory impairment in streptozotocin-induced rat model of sporadic alzheimer’s disease by repressing FoxO1 gene expression.Sci. Rep.20251512729310.1038/s41598‑025‑12426‑4 40715349
    [Google Scholar]
18. HaratizadehS. NematiM. BasiriM. NozariM. Erythropoietin and glial cells in central and peripheral nervous systems.Mol. Biol. Rep.2024511106510.1007/s11033‑024‑09997‑2 39422776
    [Google Scholar]
19. IbrahimW.W. SayedR.H. AbdelhameedM.F. Neuroprotective potential of Erigeron bonariensis ethanolic extract against ovariectomized/D-galactose-induced memory impairments in female rats in relation to its metabolite fingerprint as revealed using UPLC/MS.Inflammopharmacology20243221091111210.1007/s10787‑023‑01418‑3 38294617
    [Google Scholar]
20. JahanR. YousafM. KhanH. Zinc ortho methyl carbonodithioate improved pre and post-synapse memory impairment via SIRT1/p-JNK pathway against scopolamine in adult mice.J. Neuroimmune Pharmacol.2023181-218319410.1007/s11481‑023‑10067‑w 37261605
    [Google Scholar]
21. MaieseK. Novel applications of trophic factors, Wnt and WISP for neuronal repair and regeneration in metabolic disease.Neural Regen. Res.201510451852810.4103/1673‑5374.155427 26170801
    [Google Scholar]
22. MaieseK. FoxO proteins in the nervous system.Anal. Cell. Pathol. (Amst.)2015201511510.1155/2015/569392 26171319
    [Google Scholar]
23. MaieseK. Cognitive impairment and dementia: Gaining insight through circadian clock gene pathways.Biomolecules2021117100210.3390/biom11071002 34356626
    [Google Scholar]
24. MaieseK. Cellular metabolism: A fundamental component of degeneration in the nervous system.Biomolecules202313581610.3390/biom13050816 37238686
    [Google Scholar]
25. MaieseK. The metabolic basis for nervous system dysfunction in Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease.Curr. Neurovasc. Res.202320331433310.2174/1567202620666230721122957 37488757
    [Google Scholar]
26. MishraP. DaviesD.A. AlbensiB.C. The interaction between NF-κB and estrogen in Alzheimer’s disease.Mol. Neurobiol.20236031515152610.1007/s12035‑022‑03152‑3 36512265
    [Google Scholar]
27. MosharafM.P. AlamK. GowJ. MahumudR.A. MollahM.N.H. Common molecular and pathophysiological underpinnings of delirium and Alzheimer’s disease: Molecular signatures and therapeutic indications.BMC Geriatr.202424171610.1186/s12877‑024‑05289‑3 39210294
    [Google Scholar]
28. PattanaikS.K. AnilP.M. JenaS. RathD. Interlinking diabetes and Alzheimer’s disease: A pathway through medicinal plant-based treatments.J. Ethnopharmacol.202535112009210.1016/j.jep.2025.120092 40484255
    [Google Scholar]
29. PoddarN.K. KhanA. FatimaF. SaxenaA. GhaleyG. KhanS. Association of mTOR pathway and conformational alterations in C-reactive protein in neurodegenerative diseases and infections.Cell. Mol. Neurobiol.20234383815383210.1007/s10571‑023‑01402‑z 37665407
    [Google Scholar]
30. SharmaC. MazumderA. A comprehensive review on potential molecular drug targets for the management of alzheimer’s disease.Cent. Nerv. Syst. Agents Med. Chem.2024241455610.2174/0118715249263300231116062740 38305393
    [Google Scholar]
31. ZhangW. HuangY. GuoX. ZhangM. YuanX. ZuH. DHCR24 reverses Alzheimer’s disease-related pathology and cognitive impairment via increasing hippocampal cholesterol levels in 5xFAD mice.Acta Neuropathol. Commun.202311110210.1186/s40478‑023‑01593‑y 37344916
    [Google Scholar]
32. ZhaoJ. WeiM. GuoM. GSK3: A potential target and pending issues for treatment of Alzheimer’s disease.CNS Neurosci. Ther.2024307e1481810.1111/cns.14818 38946682
    [Google Scholar]
33. AbdallaM.M.I. Insulin resistance as the molecular link between diabetes and Alzheimer’s disease.World J. Diabetes20241571430144710.4239/wjd.v15.i7.1430 39099819
    [Google Scholar]
34. AminiJ. SanchooliN. MilajerdiM.H. BaeeriM. HaddadiM. SanadgolN. The interplay between tauopathy and aging through interruption of UPR/Nrf2/autophagy crosstalk in the Alzheimer’s disease transgenic experimental models.Int. J. Neurosci.2024134101049106710.1080/00207454.2023.2210409 37132251
    [Google Scholar]
35. ChongthamA. RamakrishnanA. FarinasM. Neocortical tau propagation is a mediator of clinical heterogeneity in Alzheimer’s disease.Mol. Psychiatry20253094194421310.1038/s41380‑025‑02998‑y 40234685
    [Google Scholar]
36. DasguptaA. KalidassK. FarishaS. SahaR. GhoshS. AmpasalaD.R. Identification of novel brain penetrant GSK-3β inhibitors toward Alzheimer’s disease therapy by virtual screening, molecular docking, dynamic simulation, and MMPBSA analysis.J. Biomol. Struct. Dyn.202412710.1080/07391102.2024.2411524 39427335
    [Google Scholar]
37. ShiravandiA. YariF. TofighN. Earlier detection of alzheimer’s disease based on a novel biomarker cis P-tau by a label-free electrochemical immunosensor.Biosensors2022121087910.3390/bios12100879 36291017
    [Google Scholar]
38. ClemmensenF.K. GramkowM.H. SimonsenA.H. Short-term variability of Alzheimer’s disease plasma biomarkers in a mixed memory clinic cohort.Alzheimers Res. Ther.20251712610.1186/s13195‑024‑01658‑7 39838483
    [Google Scholar]
39. HunjanG. AranK.R. Role of mGluR7 in Alzheimer’s disease: Pathophysiological insights and therapeutic approaches.Inflammopharmacology20253362977299510.1007/s10787‑025‑01765‑3 40316832
    [Google Scholar]
40. CiL. YangX. GuX. Cystathionine γ-lyase deficiency exacerbates CCl4-induced acute hepatitis and fibrosis in the mouse liver.Antioxid. Redox Signal.201727313314910.1089/ars.2016.6773 27848249
    [Google Scholar]
41. CuiW. MatsunoK. IwataK. NOX1/nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase promotes proliferation of stellate cells and aggravates liver fibrosis induced by bile duct ligation.Hepatology201154394995810.1002/hep.24465 21618578
    [Google Scholar]
42. DuttaR.K. JunJ. DuK. DiehlA.M. Hedgehog signaling: Implications in liver pathophysiology.Semin. Liver Dis.202343441842810.1055/a‑2187‑3382 37802119
    [Google Scholar]
43. JianY WangJ DongS Wnt-induced secreted protein 1/CCN4 in liver fibrosis both in vitro and in vivo.Clinical Lab20146001/2014293510.7754/Clin.Lab.2013.12103524600972
    [Google Scholar]
44. JunJ.I. LauL.F. Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets.Nat. Rev. Drug Discov.2011101294596310.1038/nrd3599 22129992
    [Google Scholar]
45. KlimontovV.V. BulumbaevaD.M. FazullinaO.N. Circulating Wnt1-inducible signaling pathway protein-1 (WISP-1/CCN4) is a novel biomarker of adiposity in subjects with type 2 diabetes.J. Cell Commun. Signal.202014110110910.1007/s12079‑019‑00536‑4 31782053
    [Google Scholar]
46. KlionskyD.J. Abdel-AzizA.K. AbdelfatahS. AbdellatifM. AbdoliA. AbelS. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).Autophagy2021171138210.1080/15548627.2020.179728033634751
    [Google Scholar]
47. KönigshoffM. KramerM. BalsaraN. WNT1-inducible signaling protein–1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis.J. Clin. Invest.2009119477278710.1172/JCI33950 19287097
    [Google Scholar]
48. MaieseK. Cognitive impairment with diabetes mellitus and metabolic disease: Innovative insights with the mechanistic target of rapamycin and circadian clock gene pathways.Expert Rev. Clin. Pharmacol.2020131233410.1080/17512433.2020.1698288 31794280
    [Google Scholar]
49. MaieseK. Wnt Signaling and WISP1 (CCN4): Critical Components in Neurovascular Disease, Blood Brain Barrier Regulation, and Cerebral Hemorrhage.Curr. Neurovasc. Res.202219437938210.2174/1567202620666221019162248 36264015
    [Google Scholar]
50. MaieseK. The impact of aging and oxidative stress in metabolic and nervous system disorders: Programmed cell death and molecular signal transduction crosstalk.Front. Immunol.202314127357010.3389/fimmu.2023.1273570 38022638
    [Google Scholar]
51. MaieseK. Cornerstone cellular pathways for metabolic disorders and diabetes mellitus: Non-coding RNAs, Wnt signaling, and AMPK.Cells20231222259510.3390/cells12222595 37998330
    [Google Scholar]
52. EshraghiM. AhmadiM. AfsharS. Enhancing autophagy in Alzheimer’s disease through drug repositioning.Pharmacol. Ther.202223710817110.1016/j.pharmthera.2022.108171 35304223
    [Google Scholar]
53. HouS.J. ZhangS.X. LiY. XuS.Y. Rapamycin responds to Alzheimer’s disease: A potential translational therapy.Clin. Interv. Aging2023181629163910.2147/CIA.S429440 37810956
    [Google Scholar]
54. MaieseK. Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR.Neural Regen. Res.201611337238510.4103/1673‑5374.179032 27127460
    [Google Scholar]
55. MaieseK. The mechanistic target of rapamycin (mTOR) and the silent mating-type information regulation 2 homolog 1 (SIRT1): oversight for neurodegenerative disorders.Biochem. Soc. Trans.201846235136010.1042/BST20170121 29523769
    [Google Scholar]
56. MaieseK. Targeting the core of neurodegeneration: FoxO, mTOR, and SIRT1.Neural Regen. Res.202116344845510.4103/1673‑5374.291382 32985464
    [Google Scholar]
57. MaieseK. Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm.Front. Biosci.202126961462710.52586/4971 34590471
    [Google Scholar]
58. TrisalA. SinghA.K. Clinical insights on caloric restriction mimetics for mitigating brain aging and related neurodegeneration.Cell. Mol. Neurobiol.20244416710.1007/s10571‑024‑01493‑2 39412683
    [Google Scholar]
59. YingC. HeY. GuoY. Application of traditional chinese medicine in alzheimer’s disease treatment: A focus on the Wnt/β-catenin pathway.Am. J. Chin. Med.20255361641168310.1142/S0192415X25500624 40744715
    [Google Scholar]
60. AfrishamR. JadidiY. MoradiN. Circulating CCN6/WISP3 in type 2 diabetes mellitus patients and its correlation with insulin resistance and inflammation: Statistical and machine learning analyses.BMC Med. Inform. Decis. Mak.202525111410.1186/s12911‑025‑02957‑1 40050813
    [Google Scholar]
61. BarchettaI. CiminiF.A. CapocciaD. WISP1 is a marker of systemic and adipose tissue inflammation in dysmetabolic subjects with or without type 2 diabetes.J. Endocr. Soc.20171666067010.1210/js.2017‑00108 29264519
    [Google Scholar]
62. Fernandez-RuizR. García-AlamánA. EstebanY. Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells.Nat. Commun.2020111598210.1038/s41467‑020‑19657‑1 33239617
    [Google Scholar]
63. KitaghendaF.K. WangJ. LiT. HongJ. YaoL. ZhuX. Normalization of WISP1 circulating level and tissue expression following metabolic and bariatric surgery using rat model.Updates Surg.20247682841284910.1007/s13304‑024‑01977‑2 39407056
    [Google Scholar]
64. LiuL. HuJ. YangL. Association of WISP1/CCN4 with risk of overweight and gestational diabetes mellitus in chinese pregnant women.Dis. Markers2020202011010.1155/2020/4934206 32377270
    [Google Scholar]
65. MaieseK. FoxO. FoxO transcription factors and regenerative pathways in diabetes mellitus.Curr. Neurovasc. Res.201512440441310.2174/1567202612666150807112524 26256004
    [Google Scholar]
66. MaieseK. Sirtuins: Developing innovative treatments for aged-related memory loss and Alzheimer’s disease.Curr. Neurovasc. Res.201915436737110.2174/1567202616666181128120003 30484407
    [Google Scholar]
67. ZhuY. FangQ. ZhouY. LuW. DuX. ShiB. Serum Wnt1-Inducible signalling pathway Protein-1 levels are associated with cerebral infarction in patients with type 2 diabetes mellitus.J. Endocrinol. Invest.202510.1007/s40618‑025‑02662‑w 40719953
    [Google Scholar]
68. MaieseK. ChongZ.Z. ShangY.C. WangS. mTOR: On target for novel therapeutic strategies in the nervous system.Trends Mol. Med.2013191516010.1016/j.molmed.2012.11.001 23265840
    [Google Scholar]
69. ChristopoulouM.E. AletrasA.J. PapakonstantinouE. StolzD. SkandalisS.S. WISP1 and macrophage migration inhibitory factor in respiratory inflammation: Novel insights and therapeutic potentials for asthma and COPD.Int. J. Mol. Sci.202425181004910.3390/ijms251810049 39337534
    [Google Scholar]
70. FuC. LuZ. ShiJ. LiuF. SuX. Knockdown of WISP1/DKK1 restrains phenotypic plasticity in esophageal squamous cell carcinoma by suppressing epithelial–mesenchymal transition and stemness.Clin. Transl. Oncol.202427258059210.1007/s12094‑024‑03639‑6 39093516
    [Google Scholar]
71. SinghK. OladipupoS.S. An overview of CCN4 (WISP1) role in human diseases.J. Transl. Med.202422160110.1186/s12967‑024‑05364‑8 38937782
    [Google Scholar]
72. SinghK. WitekM. BrahmbhattJ. McEntireJ. ThirunavukkarasuK. OladipupoS.S. Stage-dependent fibrotic gene profiling of WISP1-mediated fibrogenesis in human fibroblasts.Cells20241323200510.3390/cells13232005 39682753
    [Google Scholar]
73. MaieseK. Stem cell guidance through the mechanistic target of rapamycin.World J. Stem Cells2015779991009 26328016
    [Google Scholar]
74. MaieseK. Biological gases, oxidative stress, artificial intelligence, and machine learning for neurodegeneration and metabolic disorders.Med. Gas Res.202515114514710.4103/mgr.MEDGASRES‑D‑24‑00059 39436188
    [Google Scholar]
75. MaieseK. Diabetes mellitus and glymphatic dysfunction: Roles for oxidative stress, mitochondria, circadian rhythm, artificial intelligence, and imaging.World J. Diabetes20251619894810.4239/wjd.v16.i1.98948 39817214
    [Google Scholar]
76. MaieseK. Anxiety and depression: Triggers for cognitive loss, alzheimer’s disease, and neurodegeneration.Curr. Neurovasc. Res.20252211810.2174/0115672026423887250627095817 40551494
    [Google Scholar]
77. Griñán-FerréC. Servin-MuñozI.V. Palomera-ÁvalosV. Changes in gene expression profile with age in SAMP8: Identifying transcripts involved in cognitive decline and sporadic Alzheimer’s disease.Genes20241511141110.3390/genes15111411 39596610
    [Google Scholar]
78. GuoT. ChenM. LiuJ. Neuropilin-1 promotes mitochondrial structural repair and functional recovery in rats with cerebral ischemia.J. Transl. Med.202321129710.1186/s12967‑023‑04125‑3 37138283
    [Google Scholar]
79. MaieseK. The bright side of reactive oxygen species: Lifespan extension without cellular demise.J. Transl. Sci.20162318518710.15761/JTS.1000138 27200181
    [Google Scholar]
80. Sanabria-de la TorreR. García-FontanaC. González-SalvatierraS. The contribution of Wnt signaling to vascular complications in type 2 diabetes mellitus.Int. J. Mol. Sci.20222313699510.3390/ijms23136995 35805996
    [Google Scholar]
81. ValléeA. ValléeJ.N. LecarpentierY. Parkinson’s disease: Potential actions of lithium by targeting the WNT/β-Catenin pathway, oxidative stress, inflammation and glutamatergic pathway.Cells202110223010.3390/cells10020230 33503974
    [Google Scholar]
82. XuJ.X. FangK. GaoX.R. LiuS. GeJ.F. Resveratrol protects SH-SY5Y cells against oleic acid-induced glucolipid metabolic dysfunction and cell injuries via the Wnt/β-catenin signalling pathway.Neurochem. Res.202146112936294710.1007/s11064‑021‑03398‑8 34260003
    [Google Scholar]
83. ZhangM. LiuQ. MengH. Ischemia-reperfusion injury: molecular mechanisms and therapeutic targets.Signal Transduct. Target. Ther.2024911210.1038/s41392‑023‑01688‑x 38185705
    [Google Scholar]
84. LiuD. ZhangM. TianJ. WNT1-inducible signalling pathway protein 1 stabilizes atherosclerotic plaques in apolipoprotein-E-deficient mice via the focal adhesion kinase/mitogen-activated extracellular signal-regulated kinase/extracellular signal-regulated kinase pathway.J. Hypertens.20224091666168110.1097/HJH.0000000000003195 35881419
    [Google Scholar]
85. AdeerjiangY. GanX.X. LiW.T. The dual role and therapeutic implications of the Wnt/β-Catenin pathway in diabetic kidney disease.Int. J. Gen. Med.2025182757276810.2147/IJGM.S524138 40458228
    [Google Scholar]
86. EhtewishH. MeslehA. PonirakisG. Blood-based proteomic profiling identifies potential biomarker candidates and pathogenic pathways in dementia.Int. J. Mol. Sci.2023249811710.3390/ijms24098117 37175824
    [Google Scholar]
87. MaieseK. New insights for oxidative stress and diabetes mellitus.Oxid. Med. Cell. Longev.2015201587596110.1155/2015/875961 26064426
    [Google Scholar]
88. MaieseK. Erythropoietin and diabetes mellitus.World J. Diabetes20156141259127310.4239/wjd.v6.i14.1259 26516410
    [Google Scholar]
89. MaieseK. Moving to the Rhythm with Clock (Circadian) Genes, Autophagy, mTOR, and SIRT1 in Degenerative Disease and Cancer.Curr. Neurovasc. Res.2017143299304 28721811
    [Google Scholar]
90. NieX. WeiX. MaH. FanL. ChenW.D. The complex role of Wnt ligands in type 2 diabetes mellitus and related complications.J. Cell. Mol. Med.202125146479649510.1111/jcmm.16663 34042263
    [Google Scholar]
91. MaieseK. The challenges for drug development: Cytokines, genes, and stem cells.Curr. Neurovasc. Res.20129423123210.2174/156720212803530690 23030554
    [Google Scholar]
92. MurahovschiV. PivovarovaO. IlkavetsI. WISP1 is a novel adipokine linked to inflammation in obesity.Diabetes201564385686610.2337/db14‑0444 25281430
    [Google Scholar]
93. TanakaS. SugimachiK. KameyamaT. Human WISP1v, a member of the CCN family, is associated with invasive cholangiocarcinoma.Hepatology20033751122112910.1053/jhep.2003.50187 12717393
    [Google Scholar]
94. WangQ.Y. FengY.J. JiR. High expression of WISP1 promotes metastasis and predicts poor prognosis in hepatocellular carcinoma.Eur. Rev. Med. Pharmacol. Sci.202024201044510451 33155200
    [Google Scholar]
95. Damstra-OddyJ.L. WarrenE.C. PerryC.J. Phytocannabinoid‐dependent mTORC1 regulation is dependent upon inositol polyphosphate multikinase activity.Br. J. Pharmacol.202117851149116310.1111/bph.15351 33347604
    [Google Scholar]
96. LiuL. LiJ. WangC. Cannabidiol attenuates methamphetamine-induced conditioned place preference in male rats and viability in PC12 cells through the Sigma1R/AKT/GSK3β/CREB signaling pathway.Am. J. Drug Alcohol Abuse202248554856110.1080/00952990.2022.2073450 35881880
    [Google Scholar]
97. BiS.Z. SunW.D. ZhuX.J. Nicotinamide N-methyltransferase in cardiovascular Diseases: Mechanistic insights and therapeutic potential.Eur. J. Med. Chem.202529511779010.1016/j.ejmech.2025.117790 40412299
    [Google Scholar]
98. ChenM. ZhangH. JiP. Therapeutic potential of ACMSD inhibitors in NAD+ deficient diseases.Drugs and Drug Candidates202541710.3390/ddc4010007
    [Google Scholar]
99. DengQ. ChenS. PeiD. Untargeted cell metabolomics and network analysis of CORT-Injured HT22 cells treated with albiflorin.J. Pharm. Biomed. Anal.202526511704410.1016/j.jpba.2025.117044 40618436
    [Google Scholar]
100. HuZ. CaiY. CaoC. Metabolome and transcriptome analyses reveal the mechanism underlying the differences in skin development between the two duck breeds during embryonic stage.Poult. Sci.2025104910540310.1016/j.psj.2025.105403 40499236
     [Google Scholar]
101. MaX. JinW. WangL. Metabolic response of Sinosolenaia oleivora to heat and drought stress using a quasi-targeted metabolomics approach.Comp. Biochem. Physiol. Part D Genomics Proteomics20255510149910.1016/j.cbd.2025.101499 40215765
     [Google Scholar]
102. MaieseK. Warming up to new possibilities with the capsaicin receptor TRPV1: mTOR, AMPK, and erythropoietin.Curr. Neurovasc. Res.2017142184189 28294062
     [Google Scholar]
103. MaieseK. New Insights for nicotinamide metabolic disease autophagy and mTOR.Front. Biosci.202025111925197310.2741/4886 32472766
     [Google Scholar]
104. MaieseK. Innovative therapeutic strategies for cardiovascular disease.EXCLI J.202322690715 37593239
     [Google Scholar]
105. MaieseK. Cognitive impairment in multiple sclerosis.Bioengineering202310787110.3390/bioengineering10070871 37508898
     [Google Scholar]
106. TraisterA. BreitmanI. Bar-LevE. Nicotinamide induces apoptosis and reduces collagen I and pro-inflammatory cytokines expression in rat hepatic stellate cells.Scand. J. Gastroenterol.200540101226123410.1080/00365520510023341 16165703
     [Google Scholar]
107. Castro-PortuguezR. SutphinG.L. Kynurenine pathway, NAD+ synthesis, and mitochondrial function: Targeting tryptophan metabolism to promote longevity and healthspan.Exp. Gerontol.202013211084110.1016/j.exger.2020.110841 31954874
     [Google Scholar]
108. DorofteiB. IlieO.D. CojocariuR.O. Minireview exploring the biological cycle of vitamin B3 and its influence on oxidative stress: Further molecular and clinical aspects.Molecules20202515332310.3390/molecules25153323 32707945
     [Google Scholar]
109. DuX. CuiZ. ZhangR. The effects of rumen-protected choline and rumen-protected nicotinamide on liver transcriptomics in periparturient dairy cows.Metabolites202313559410.3390/metabo13050594 37233635
     [Google Scholar]
110. MaieseK. Nicotinamide: Oversight of metabolic dysfunction through SIRT1, mTOR, and clock genes.Curr. Neurovasc. Res.202117576578310.2174/18755739MTEx2NDIjx 33183203
     [Google Scholar]
111. MaieseK. Nicotinamide as a foundation for treating neurodegenerative disease and metabolic disorders.Curr. Neurovasc. Res.202118113414910.2174/18755739MTEzaMDMw2 33397266
     [Google Scholar]
112. Osorio AlvesJ. Matta PereiraL. Cabral Coutinho do Rego MonteiroI. Strenuous acute exercise induces slow and fast twitch-dependent NADPH oxidase expression in rat skeletal muscle.Antioxidants20209157710.3390/antiox9010057 31936265
     [Google Scholar]
113. Ramírez-CruzA. Gómez-GonzálezB. Baiza-GutmanL.A. Nicotinamide, an acetylcholinesterase uncompetitive inhibitor, protects the blood‒brain barrier and improves cognitive function in rats fed a hypercaloric diet.Eur. J. Pharmacol.202395917606810.1016/j.ejphar.2023.176068 37775016
     [Google Scholar]
114. RehmanI.U. KhanA. AhmadR. Neuroprotective effects of nicotinamide against MPTP-induced parkinson’s disease in mice: Impact on oxidative stress, neuroinflammation, Nrf2/HO-1 and TLR4 signaling pathways.Biomedicines20221011292910.3390/biomedicines10112929 36428497
     [Google Scholar]
115. BraidyN. LiuY. NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis.Exp. Gerontol.202013211083110.1016/j.exger.2020.110831 31917996
     [Google Scholar]
116. Goulart Nacácio e SilvaS. OcchiuttoM.L. CostaV.P. The use of nicotinamide and nicotinamide riboside as an adjunct therapy in the treatment of glaucoma.Eur. J. Ophthalmol.20233351801181510.1177/11206721231161101 36916064
     [Google Scholar]
117. JobstM. KissE. GernerC. MarkoD. Del FaveroG. Activation of autophagy triggers mitochondrial loss and changes acetylation profile relevant for mechanotransduction in bladder cancer cells.Arch. Toxicol.202397121723310.1007/s00204‑022‑03375‑2 36214828
     [Google Scholar]
118. MaieseK. ChongZ.Z. Nicotinamide: Necessary nutrient emerges as a novel cytoprotectant for the brain.Trends Pharmacol. Sci.200324522823210.1016/S0165‑6147(03)00078‑6 12767721
     [Google Scholar]
119. WangX.Y. LiuK.J. ZhangF.Y. XiangB. Nicotinamide mitigates radiation injury in submandibular gland by protecting mitochondrial structure and functions.J. Oral Pathol. Med.202251980180910.1111/jop.13347 35996988
     [Google Scholar]
120. WasserfurthP. NeblJ. RühlingM.R. Impact of dietary modifications on plasma sirtuins 1, 3 and 5 in older overweight individuals undergoing 12-weeks of circuit training.Nutrients20211311382410.3390/nu13113824 34836079
     [Google Scholar]
121. YuanX. LiuY. BijonowskiB.M. NAD+/NADH redox alterations reconfigure metabolism and rejuvenate senescent human mesenchymal stem cells in vitro.Commun. Biol.20203177410.1038/s42003‑020‑01514‑y 33319867
     [Google Scholar]
122. ZhangG.Z. DengY.J. XieQ.Q. Sirtuins and intervertebral disc degeneration: Roles in inflammation, oxidative stress, and mitochondrial function.Clin. Chim. Acta2020508334210.1016/j.cca.2020.04.016 32348785
     [Google Scholar]
123. NejabatiH.R. SamadiN. ShahnaziV. Nicotinamide and its metabolite N1-Methylnicotinamide alleviate endocrine and metabolic abnormalities in adipose and ovarian tissues in rat model of Polycystic Ovary Syndrome.Chem. Biol. Interact.202032410909310.1016/j.cbi.2020.109093 32298659
     [Google Scholar]
124. BabighianS. GattazzoI. ZanellaM.S. Nicotinamide: Bright potential in glaucoma management.Biomedicines2024128165510.3390/biomedicines12081655 39200120
     [Google Scholar]
125. MillerR. WentzelA.R. RichardsG.A. COVID-19: NAD+ deficiency may predispose the aged, obese and type2 diabetics to mortality through its effect on SIRT1 activity.Med. Hypotheses202014411004410.1016/j.mehy.2020.110044 32758884
     [Google Scholar]
126. SharmaN. ShandilyaA. KumarN. MehanS. Dysregulation of SIRT-1 signaling in multiple sclerosis and neuroimmune disorders: A systematic review of SIRTUIN activators as potential immunomodulators and their influences on other dysfunctions.Endocr. Metab. Immune Disord. Drug Targets202121101845186810.2174/1871530321666210309112234 33687904
     [Google Scholar]
127. YeM. ZhaoY. WangY. NAD(H)-loaded nanoparticles for efficient sepsis therapy via modulating immune and vascular homeostasis.Nat. Nanotechnol.202217888089010.1038/s41565‑022‑01137‑w 35668170
     [Google Scholar]
128. AtalayS. GęgotekA. DominguesP. SkrzydlewskaE. Protective effects of cannabidiol on the membrane proteins of skin keratinocytes exposed to hydrogen peroxide via participation in the proteostasis network.Redox Biol.20214610207410.1016/j.redox.2021.102074 34298466
     [Google Scholar]
129. PereiraG.J.S. LeãoA.H.F.F. ErustesA.G. Pharmacological modulators of autophagy as a potential strategy for the treatment of COVID-19.Int. J. Mol. Sci.2021228406710.3390/ijms22084067 33920748
     [Google Scholar]
130. GuoW. QianL. ZhangJ. Sirt1 overexpression in neurons promotes neurite outgrowth and cell survival through inhibition of the mTOR signaling.J. Neurosci. Res.201189111723173610.1002/jnr.22725 21826702
     [Google Scholar]
131. LiW. ZhuL. RuanZ.B. WangM.X. RenY. LuW. Nicotinamide protects chronic hypoxic myocardial cells through regulating mTOR pathway and inducing autophagy.Eur. Rev. Med. Pharmacol. Sci.2019231255035511 31298404
     [Google Scholar]
132. TabibzadehS. Signaling pathways and effectors of aging.Front. Biosci.2021261509610.2741/4889 33049665
     [Google Scholar]
133. ZhangS. CaiG. FuB. SIRT1 is required for the effects of rapamycin on high glucose-inducing mesangial cells senescence.Mech. Ageing Dev.2012133638740010.1016/j.mad.2012.04.005 22561310
     [Google Scholar]
134. Asir A,R.V. Unlocking the therapeutic potential of protein kinase inhibitors in neurodegenerative and psychiatric disorders.Explor. Drug Sci.2025310089210.37349/eds.2025.100892
     [Google Scholar]
135. ElbazE.M. IbrahimS.M. RashadE. YasinN.A.E. GhaiadH.R. MehanaN.A. Therapeutic role of 1-theanine in mitigating cognitive dysfunction and neuropathology in scopolamine-treated mice.ACS Chem. Neurosci.202516132528254510.1021/acschemneuro.5c00351 40504752
     [Google Scholar]
136. FedorA. BryniarskiK. NazimekK. mTOR signaling in macrophages: All depends on the context.Int. J. Mol. Sci.20252615759810.3390/ijms26157598 40806725
     [Google Scholar]
137. JiangT. DuP. LiuD. Exploring the glucose-lowering and anti-inflammatory immune mechanism of artemether by AMPK/mTOR pathway and microbiome based on multi-omics.Front. Pharmacol.202516152043910.3389/fphar.2025.1520439 40046742
     [Google Scholar]
138. MubarakH.M. RacetteB.A. KillionJ.A. Exploring the neuroprotective potential of immunosuppressants in Parkinson’s disease.Parkinsonism Relat. Disord.202513210729410.1016/j.parkreldis.2025.107294 39874798
     [Google Scholar]
139. SantosG.X. dos Anjos-GarciaT. VieiraA.C.J. GaldinoG. Spinal involvement of TRPV1 and PI3K/AKT/mTOR pathway during chronic postoperative pain in mice.Brain Sci.20251515310.3390/brainsci15010053 39851421
     [Google Scholar]
140. TangJ. LuL. YuanJ. FengL. Exercise-induced activation of SIRT1/BDNF/mTORC1 signaling pathway: A novel mechanism to reduce neuroinflammation and improve post-stroke depression.Actas Esp. Psiquiatr.202553236637810.62641/aep.v53i2.1838 40071363
     [Google Scholar]
141. XiaW. XieX. WangC. ZhangL. CaiY. GeZ. Reduction in cardiac STAT3 phosphorylation at site ser-727 subsequent to mTOR overactivation exacerbated myocardial ischemia reperfusion injury in type 1 diabetic rats.Fortune J. Health Sci.2025860761710.26502/fjhs.313
     [Google Scholar]
142. YongJ. KimH. LeeE. JungY. Regulation of transcriptome plasticity by mTOR signaling pathway.Exp. Mol. Med.20255781623163010.1038/s12276‑025‑01508‑y 40804480
     [Google Scholar]
143. ZeidanM.A. AlkabbaniM.A. GiovannuzziS. Shooting an arrow against convulsion: Novel triazole-grafted benzenesulfonamide derivatives as carbonic anhydrase II and VII inhibitors.J. Med. Chem.20256888873889310.1021/acs.jmedchem.5c00526 40237575
     [Google Scholar]
144. MaieseK. Taking aim at Alzheimer’s disease through the mammalian target of rapamycin.Ann. Med.201446858759610.3109/07853890.2014.941921 25105207
     [Google Scholar]
145. MaieseK. mTOR: Driving apoptosis and autophagy for neurocardiac complications of diabetes mellitus.World J. Diabetes20156221722410.4239/wjd.v6.i2.217 25789103
     [Google Scholar]
146. MaieseK. Targeting molecules to medicine with mTOR, autophagy and neurodegenerative disorders.Br. J. Clin. Pharmacol.20168251245126610.1111/bcp.12804 26469771
     [Google Scholar]
147. MaieseK. Dysregulation of metabolic flexibility: The impact of mTOR on autophagy in neurodegenerative disease.Int. Rev. Neurobiol.202015513510.1016/bs.irn.2020.01.009 32854851
     [Google Scholar]
148. MaieseK. Prospects and perspectives for WISP1 (CCN4) in diabetes mellitus.Curr. Neurovasc. Res.202017332733110.2174/1567202617666200327125257 32216738
     [Google Scholar]
149. Gonzalez-AlcocerA. Gopar-CuevasY. Soto-DominguezA. Peripheral tissular analysis of rapamycin’s effect as a neuroprotective agent in vivo.Naunyn Schmiedebergs Arch. Pharmacol.2022395101239125510.1007/s00210‑022‑02276‑6 35895156
     [Google Scholar]
150. MaieseK. ChongZ.Z. ShangY.C. WangS. Novel directions for diabetes mellitus drug discovery.Expert Opin. Drug Discov.201381354810.1517/17460441.2013.736485 23092114
     [Google Scholar]
151. WuZ. LiH. ZhangY. Liver transcriptome analyses of acute poisoning and recovery of male ICR mice exposed to the mushroom toxin α-amanitin.Arch. Toxicol.20229661751176610.1007/s00204‑022‑03278‑2 35384471
     [Google Scholar]
152. ZhouQ. TangS. ZhangX. ChenL. Targeting PRAS40: A novel therapeutic strategy for human diseases.J. Drug Target.202129770371510.1080/1061186X.2021.1882470 33504218
     [Google Scholar]