Neurosteroids and oxysterols as potential therapeutic agents for glaucoma and Alzheimer's disease.
Neurosteroids and oxysterols as potential therapeutic agents for glaucoma and Alzheimer's disease.
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DOI：
10.4172/neuropsychiatry.1000356
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发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Izumi, Yukitoshi
中科院分区：
文献类型：
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作者：
Ishikawa, Makoto;Yoshitomi, Takeshi;Izumi, Yukitoshi
青光眼是世界范围内视力损害的最常见原因之一，并且涉及对视网膜神经节细胞（RGC）的选择性损伤，导致连接视网膜与视觉皮层的神经通路变性。令人感兴趣的是，阿尔茨海默病（AD）中的病理变化的相似性已被描述，阿尔茨海默病是老年人进行性记忆丧失和痴呆的最常见原因。淀粉样蛋白-β（Abeta）和过度磷酸化的tau的积累被认为有助于阿尔茨海默病中的凋亡性神经元死亡，并且类似的变化与青光眼中的凋亡性RGC死亡有关。青光眼和阿尔茨海默病也都缺乏有效的治疗方法，这促使人们寻找新的治疗干预措施。神经类固醇（NS）（包括氧固醇）是在神经系统中由胆固醇合成的内源性分子，其可以调节谷氨酸和GABA受体，谷氨酸和GABA受体分别是大脑中快速兴奋性和抑制性神经传递的主要介质。由于谷氨酸和GABA神经递质系统的变化有助于AD和青光眼的发病机制，NS是这些疾病的可能治疗靶点。在这篇综述中，我们提出了最近的证据支持阿尔茨海默病和青光眼之间的病理联系，并专注于可能的作用，在这些疾病中的NS和如何NS可能被开发用于治疗目的。
Glaucoma is one of the most frequent causes of visual impairment worldwide and involves selective damage to retinal ganglion cells (RGCs) resulting in degeneration of neural pathways connecting retina to visual cortex. It is of interest that similarities in pathological changes have been described in Alzheimer's disease (AD), the most common cause of progressive memory loss and dementia in older people. Accumulation of amyloid-beta (Abeta) and hyperphosphorylated tau is thought to contribute to apoptotic neuronal death in Alzheimer's disease, and similar changes have been linked to apoptotic RGC death in glaucoma. Both glaucoma and Alzheimer's disease also suffer from a lack of effective treatments prompting a search for novel therapeutic interventions. Neurosteroids (NSs) (including oxysterols) are endogenous molecules synthesized in the nervous system from cholesterol that can modulate glutamate and GABA receptors, the primary mediators of fast excitatory and inhibitory neurotransmission in the brain, respectively. Because changes in the glutamate and GABA neurotransmitter systems contribute to the pathogenesis of AD and glaucoma, NSs are possible therapeutic targets for these disorders. In this review, we present recent evidence supporting pathological links between Alzheimer's disease and glaucoma, and focus on the possible role of NSs in these diseases and how NSs might be developed for therapeutic purposes.