小分子和阿尔茨海默氏症：错误折叠、新陈代谢和成像

Title:Small Molecules and Alzheimer’s Disease: Misfolding, Metabolism and Imaging

Volume: 12 Issue: 5

Author(s): Viharkumar Patel, Xueli Zhang, Nicolas A. Tautiva, Akwe N. Nyabera, Opeyemi O. Owa, , Melvin Baidya, Hee Chang Sung, Pardeep S. Taunk, Shahrzad Abdollahi, Stacey Charles and Rachel A. Gonnella, Nikhita Gadi, Karen T. Duong, Janelle N. Fawver, Chongzhao Ran, Tuula O. Jalonen and Ian V.J. Murray

Affiliation:

关键词: 阿尔茨海默氏症；淀粉样蛋白绑定；动物模型；三磷酸腺苷；脑成像技术；近红外荧光；小化合物。

摘要: Small molecule interactions with amyloid proteins have had a huge impact in Alzheimer's disease (AD), especially in three specific areas: amyloid folding, metabolism and brain imaging. Amyloid plaque amelioration or prevention have, until recently, driven drug development, and only a few drugs have been advanced for use in AD. Amyloid proteins undergo misfolding and oligomerization via intermediates, eventually forming protease resistant amyloid fibrils. These fibrils accumulate to form the hallmark amyloid plaques and tangles of AD. Amyloid binding compounds can be grouped into three categories, those that: i) prevent or reverse misfolding, ii) halt misfolding or trap intermediates, and iii) accelerate the formation of stable and inert amyloid fibrils. Such compounds include hydralazine, glycosaminoglycans, curcumin, beta sheet breakers, catecholamines, and ATP. The versatility of amyloid binding compounds suggests that the amyloid structure may serve as a scaffold for the future development of sensors to detect such compounds. Metabolic dysfunction is one of the earliest pathological features of AD. In fact, AD is often referred to as type 3 diabetes due to the presence of insulin resistance in the brain. A recent study indicates that altering metabolism improves cognitive function. While metabolic reprogramming is one therapeutic avenue for AD, it is more widely used in some cancer therapies. FDA approved drugs such as metformin, dichloroacetic acid (DCA), and methylene blue can alter metabolism. These drugs can therefore be potentially applied in alleviating metabolic dysfunction in AD. Brain imaging has made enormous strides over the past decade, offering a new window to the mind. Recently, there has been remarkable development of compounds that have the ability to image both types of pathological amyloids: tau and amyloid beta. We have focused on the low cost, simple to use, near infrared fluorescence (NIRF) imaging probes for amyloid beta (Aβ), with specific attention on recent developments to further improve contrast, specificity, and sensitivity. With advances in imaging technologies, such fluorescent imaging probes will open new diagnostic avenues.

Cite this article as:

Viharkumar Patel, Xueli Zhang, Nicolas A. Tautiva, Akwe N. Nyabera, Opeyemi O. Owa , , Melvin Baidya, Hee Chang Sung, Pardeep S. Taunk, Shahrzad Abdollahi, Stacey Charles and Rachel A. Gonnella, Nikhita Gadi, Karen T. Duong, Janelle N. Fawver, Chongzhao Ran, Tuula O. Jalonen and Ian V.J. Murray , Small Molecules and Alzheimer’s Disease: Misfolding, Metabolism and Imaging, Current Alzheimer Research 2015; 12 (5) . https://dx.doi.org/10.2174/1567205012666150504145646