Peroxisome proliferator-activated receptors (PPARs) agonists as promising neurotherapeutics

被引：0
作者：
Ghannam, Iman A. Y. [1 ]
Hassan, Rasha M. [2 ]
Abdel-Maksoud, Mohammed S. [2 ]
机构：
[1] Natl Res Ctr, Pharmaceut & Drug Ind Res Inst, Chem Nat & Microbial Prod Dept, Cairo 12622, Egypt
[2] Natl Res Ctr, Pharmaceut & Drug Ind Res Inst, Med & Pharmaceut Chem Dept, PO 12622, Giza, Egypt
来源：
BIOORGANIC CHEMISTRY | 2025年 / 156卷
关键词：
PPARs; Neurodegenerative Disorders; Mitochondrial Biogenesis; Autophagy; Neuroprotection; MODERATE ALZHEIMERS-DISEASE; TRANSGENIC MOUSE MODEL; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MILD COGNITIVE IMPAIRMENT; AMYLOID PRECURSOR PROTEIN; NF-KAPPA-B; GAMMA AGONIST; PARKINSONS-DISEASE; DELTA AGONIST;
D O I：
10.1016/j.bioorg.2025.108226
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Neurodegenerative disorders are characterized by a continuous neurons loss resulting in a wide range of pathogenesis affecting the motor impairment. Several strategies are outlined for therapeutics of synthetic and natural PPARs agonists in some neurological disorders; Parkinson's disease (PD), Alzheimer's disease (AD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). The aim of this review is to provide a recent update of the previously reported studies, and reviews dealing with the medicinal chemistry of PPARs and their agonists, and to highlight the outstanding advances in the development of both synthetic compounds including; PPAR alpha agonists (fibrates), PPAR gamma agonists (thiazolidindiones), and PPAR beta/delta agonists either as sole or dual acting PPAR full or pan agonists, in addition to the natural phytochemicals; acids, cannabinoids, and flavonoids for their different neuroprotection effects in the previously mentioned neurodegenerative disorders (PD, AD, MS, ALS, and HD). Moreover, this review reports the diverse pre-clinical and clinical studies of PPARs agonists in the neurodegenerative diseases via cellular, and animal models and human.
引用
收藏
页数：17
相关论文
共 136 条
  • [91] Santos M.J., Quintanilla R.A., Toro A., Grandy R., Dinamarca M.C., Godoy J.A., Inestrosa N.C., Peroxisomal proliferation protects from beta-amyloid neurodegeneration, J. Biol. Chem., 280, pp. 41057-41068, (2005)
  • [92] Inestrosa N.C., Carvajal F.J., Zolezzi J.M., Tapia-Rojas C., Serrano F., Karmelic D., Toledo E.M., Toro A., Toro J., Santos M.J., Peroxisome proliferators reduce spatial memory impairment, synaptic failure, and neurodegeneration in brains of a double transgenic mice model of Alzheimer's disease, J. Alzheimers Dis., 33, pp. 941-959, (2013)
  • [93] Tufano M., Pinna G., Is there a future for PPARs in the treatment of neuropsychiatric disorders?, Molecules, 25, (2020)
  • [94] Qu X.X., He J.H., Cui Z.Q., Yang T., Sun X.H., PPAR-α agonist GW7647 protects against oxidative stress and iron deposit via GPx4 in a transgenic mouse model of Alzheimer's diseases, ACS Chem. Nerosci., 13, pp. 207-216, (2022)
  • [95] Harrington C., Sawchak S., Chiang C., Davies J., Donovan C., Saunders A.M., Irizarry M., Jeter B., Zvartau-Hind M., van Dyck C.H., Gold M., Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: two phase 3 studies, Curr. Alzheimer Res., 8, pp. 592-606, (2011)
  • [96] Gold M., Alderton C., Zvartau-Hind M., Egginton S., Saunders A.M., Irizarry M., Craft S., Landreth G., Linnamagi U., Sawchak S., Rosiglitazone monotherapy in mild-to-moderate Alzheimer's disease: results from a randomized, double-blind, placebo-controlled phase III study, Dement. Geriatr. Cogn. Disord., 30, pp. 131-146, (2010)
  • [97] Sarathlal K.C., Kakoty V., Krishna K.V., Dubey S.K., Chitkara D., Taliyan R., Neuroprotective efficacy of co-encapsulated rosiglitazone and vorinostat nanoparticle on streptozotocin induced mice model of Alzheimer disease, ACS Chem. Nerosci., 12, pp. 1528-1541, (2021)
  • [98] Heneka M.T., Fink A., Doblhammer G., Effect of pioglitazone medication on the incidence of dementia, Ann. Neurol., 78, pp. 284-294, (2015)
  • [99] Chou P.S., Ho B.L., Yang Y.H., Effects of pioglitazone on the incidence of dementia in patients with diabetes, J. Diabetes Complications, 31, pp. 1053-1057, (2017)
  • [100] Kummer M.P., Heneka M.T., PPARs in Alzheimer's disease, PPAR Res., 2008, (2008)
567891011121314