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HKUST Discovers a Novel Molecular Target and Unveils New Therapeutic Strategy for Alzheimer's Disease

香港科技大學發現新的分子標靶 有助治療阿爾茲海默症

    PNAS

Blockade of EphA4 signaling ameliorates hippocampal synaptic dysfunctions in mouse models of Alzheimer's disease
(Reference reading)

    South China Morning Post

 

Hong Kong researchers may have found way to combat Alzheimer's disease

Researchers believe they have found a way to slow the progress of Alzheimer's disease, one of the leading causes of death among elderly people.

A team from the University of Science and Technology has identified a protein found on the surface of brain cells that they believe causes the disease. They found that when over-activated, the protein EphA4 causes deterioration in learning and memory abilities.

The team has also identified a molecule in the Chinese medicinal herb gou teng (uncaria rhynchophylla) that inhibits the protein's activity.

Developing a drug with the use of the molecule, rhynchophylline, could take another five to 10 years, according to Professor Nancy Ip Yuk-yu, who led the research.

"We hope our method will be able to target early abnormal changes in Alzheimer's patients and can slow the progression of the disease," she said yesterday.

In 2009, Alzheimer's disease affected about 103,000 people in Hong Kong; by 2039 it is expected to affect 332,000. Early symptoms of the disease include memory loss and a decline in thinking abilities. In its advanced stages, the disease can be fatal.

While some drugs target Alzheimer's symptoms, there are none as yet that address its cause, which is not fully understood.

The team has been studying the brain cell protein for more than 10 years. They found that its over-activation impaired the signalling between brain cells.

About three years ago, the team used rhynchophylline to improve the memory of mice.

The researchers used two groups of about 20 mice - one with Alzheimer's, one without. Each group was divided into two - one was fed with rhynchophylline for three to four months and one was not.

The mice were then put into a wading pool that contained a resting platform.

When the platform was later removed, the memory of each mouse was measured by the length of time it stayed in the section of the pool where the platform had previously been placed.

Mice which had Alzheimer's and received the treatment showed improved memory; healthy mice which received the treatment did not improve.

The study was published in Proceedings of the National Academy of Sciences of the United States of America last month.

The team is now seeking to work with drug manufacturers and medical schools, and will continue to study the brain cell protein to see whether it plays a role in other diseases.

Ip discouraged patients from eating the herb, saying the levels of rhynchophylline would be too small to have an effect.

    鳳凰衛視

香港科技大學發現治療腦退化症新分子靶 - 時事直通車

    蘋果日報

科大實驗改善老鼠記憶 中藥材鉤藤 腦退化救星

治療腦退化症有新突破。香港科技大學研究團隊從中藥鉤藤提取天然化合物,可抑制腦神經細胞蛋白異常活化,於老鼠身上證明可改善記憶及學習能力,有望5至10年內發展成治療腦退化症藥物。

俗稱腦退化症的阿爾兹海默症,患者會出現記憶、推理及判斷力衰退喪失等認知障礙。目前已知病因之一,是腦神經細胞突觸上的蛋白EphA4,被澱粉樣蛋白(Aβ)過度激活,減低神經細胞間通訊能力所致。

科大理學院院長、分子神經科學國家重點實驗室主任葉玉如領導的團隊,發現中藥鉤藤含有的鉤藤鹼(Rhynchophylline),分子結構與Aβ接近,能與EphA4結合停止其活性,可作為分子標靶,抑制過度激活導致患者認知障礙。

團隊又用老鼠進行「水迷宮實驗」,訓練在水池中尋找定點目標物,在熟悉後再將其取走,觀察老鼠尋找路徑,測試記憶能力。結果顯示,大部份腦退化老鼠,在服用鉤藤鹼4個月後,記憶及學習能力均達正常水平,針對神經反應的電生理測試(Electrophysiological Study)更在三周內回復正常。

藥物最快5年後面世

葉玉如表示,新療法是針對腦退化症的機理,有望減慢甚至停止病情惡化;鉤藤在中醫有保護腦神經、治療癲癇症的功效,惟當中鉤藤鹼含量極低,不建議直接服用。她又指,現時全球有3,500萬人患有腦退化症,每8位65歲以上長者就有1位患有該症,估計2050年會增至1.2億人。

團隊未來會尋求與醫學院及藥廠合作,進行臨床試驗及簡化化合物合成程序,預計需5至10年,方可正式作醫療用途。 老年痴呆症協會主席吳義銘表示,現時用於治療腦退化症的藥物作用不大,「有啲用,但唔係好犀利」,只能輕微舒緩如記性差、不能集中精神等症狀。對於新療法,吳稱「聽住先」,因過往有太多類似消息,但多年來始終未有突破。

中大何善衡老年學及老年病學研究中心副總監郭志銳稱,新療法有無成效要進行臨床試驗始有分曉,因老鼠的阿爾兹海默症與人不完全相同,「好多時喺老鼠有效但係臨床未有成效」。他指現時藥物主要是補充腦神經傳遞訊息介質,及壓抑過度活躍反應,於短期內有效,只屬舒緩性質。

    東方日報

科大研究:中藥鉤藤減慢腦退化

腦退化症(又稱老人癡呆症)可致記憶力衰退及認知障礙,嚴重影響患者日常生活。香港科技大學最新研究發現,中藥鉤藤含化合物「鉤藤鹼」,或助減慢腦退化,改善記憶力。專家解釋,腦退化症與一種蛋白過度激活有關,鉤藤鹼可抑制蛋白活性。今次研究結果有助科學家研製新藥治療腦退化症,為患者帶來曙光。

科大理學院院長兼生命科學講座教授葉玉如,三年前起帶領團隊研究鉤藤鹼治療腦退化症的成效。研究員由鉤藤提取化合物鉤藤鹼,每日餵給患腦退化症老鼠。三至四個月後,老鼠記憶力比對照組病鼠大為改善。

實驗先安排病鼠在水中游泳,並設平台讓病鼠休息。研究員及後取走平台,發現病鼠懂「認路」,較多時間徘徊在原設平台的範圍,想找到平台「抖抖」;對照組的病鼠則傾向周圍游。

成效及安全性仍待確定

葉玉如指,腦退化症患者出現認知障礙等問題,主因是腦神經內的澱粉樣蛋白影響。蛋白過度激活名為「EphA4」的蛋白,減低神經細胞傳遞訊號能力。鉤藤鹼能抑制EphA4活性,相信有助減慢腦退化。中醫利用鉤藤治療心血管病及腦癇症,文獻亦指鉤藤鹼可保護神經。

葉玉如強調,鉤藤僅含微量鉤藤鹼,不建議市民自行煲藥「補腦」,鉤藤鹼對治療腦退化症的成效及安全性仍待大型研究確定。

 
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