PPAR? and its ligand erucic acid may act anti-tumoral, neuroprotective, and myelin protective in neuroblastoma, glioblastoma, and Parkinson?s disease

被引:32
作者
Altinoz, Meric A. [1 ]
Elmaci, Ilhan [2 ]
Hacimuftuoglu, Ahmet [3 ]
Ozpinar, Alp [4 ]
Hacker, Emily [4 ]
Ozpinar, Aysel [1 ]
机构
[1] Acibadem Univ, Dept Biochem, Istanbul, Turkey
[2] Acibadem Hosp, Dept Neurosurg, Istanbul, Turkey
[3] Ataturk Univ, Dept Pharmacol, Erzurum, Turkey
[4] Pittsburgh Univ, Dept Neurosurg, Pittsburgh, PA USA
关键词
PPAR; Erucic acid; Melanoma; Neuroblastoma; Glioblastoma; Parkinson ?s disease; ACTIVATED-RECEPTOR-DELTA; FATTY-ACIDS; DOPAMINERGIC-NEURONS; BREAST-CANCER; LORENZOS OIL; RAT MODEL; THROMBIN; CELL; BETA/DELTA; BRAIN;
D O I
10.1016/j.mam.2020.100871
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
In this review study, we focus on potential benefits of the transcription factor PPAR? and its ligand erucic acid (EA) in management of neuroectodermal tumors and Parkinson?s Disease. PPAR? is a nuclear receptor and transcription factor that induces myelination, promotes oligodendroglial and neuronal differentiation, and possess anti-neuroinflammatory properties. While both pro-tumorigenic and anti-tumorigenic effects have been described for PPAR?, we propose that PPAR? may perform a predominantly anticancer role in tumors originating from the neuroectoderm. PPAR? ligand-activation via oleic acid and GW501516, or overexpression of PPAR?, elicits profound antitumor actions in neuroblastoma and melanoma. In glioblastomas, there is evidence indicating a differentiation failure of O2A (oligodendroglial-astrocytic biprogenitor) cells and it has been shown that EA reduced DNA synthesis in C6 rat glioblastoma spheroid cultures in clinically achievable concentrations. EA is a ?9 fatty acid which is being used in the treatment of adrenoleukodystrophy. EA is widely consumed in Asian countries via ingestion of cruciferous vegetables including mustard and rapeseed oil. EA also exerts antioxidant and anti-inflammatory activities. Recent studies of Parkinson?s Disease (PD) have implicated demyelination, white matter pathology, oligodendroglial injury, and neural inflammation in the underlying pathophysiology. In the rotenone PD model in rats, PPAR? ligand GW501516 saves dopaminergic neurons during injury induced by chemical toxins and improves behavioral functioning in PD via alleviation of endoplasmic reticulum stress. PPAR? agonists also reduce the NLRP3 inflammasome-associated neural inflammation in the MPTP PD model in mice. Herein, we propose that PPAR? and its ligand EA highly deserve to be studied in animal models of neuroblastoma, glioblastoma, and PD.
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页数:10
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