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Neuroprotective effects of PPARy agonists against cellular oxidative insults

机译:PPARγ激动剂对细胞氧化损伤的神经保护作用

摘要

The current invention comprises compositions and methods for protecting a neuronal cell of a subject from a toxic insult. The method includes delivering an effective amount of a neuroprotective compound to the neuronal cells before or after the toxic insult. The neuroprotective compounds contain a peroxisome proliferator activated receptor (“PPAR-&ggr;”) binding moiety with either a phenolic ring moiety or a prostaglandin (“PG”) with a reactive &agr;,&bgr;-unsaturated carbonyl group on the cyclopentenone ring. Other novel compounds are also disclosed. The toxic insult that impinges upon the neuronal cell may be an acute process, or chronic disease process. Oxidative stress (e.g. hydrogen peroxide, and glutamate), injury, and secondary physiological responses to injury are among the acute processes discussed. Clinical disease processes that comprise oxidative stress, inflammatory responses, strokes, Alzheimer's disease, dementia, and Parkinson's disease are also addressed. Because PPAR-&ggr; agonists are used to treat type II diabetes, a condition that leads to neurological complications, a single agent that can target both conditions is of great therapeutic value.
机译:本发明包括用于保护受试者的神经细胞免受毒性伤害的组合物和方法。该方法包括在毒性损伤之前或之后将有效量的神经保护化合物递送至神经元细胞。所述神经保护性化合物包含过氧化物酶体增殖物激活的受体(“ PPAR-”)结合部分,所述结合部分具有酚环部分或前列腺素(“ PG”),所述前列腺素在其上具有反应性α,β-不饱和羰基。环戊烯酮环。还公开了其他新颖的化合物。撞击神经元细胞的毒性伤害可能是急性过程,也可能是慢性疾病过程。氧化应激(例如过氧化氢和谷氨酸),损伤和对损伤的继发生理反应是所讨论的急性过程。还解决了包括氧化应激,炎症反应,中风,阿尔茨海默氏病,痴呆和帕金森氏病在内的临床疾病过程。因为PPAR-&ggr;激动剂用于治疗II型糖尿病(一种导致神经系统并发症的疾病),可以同时针对这两种疾病的单一药物具有巨大的治疗价值。

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