从双抑制剂到多靶点药物对阿尔茨海默病的进一步治疗

Title:From Bitopic Inhibitors to Multitarget Drugs for the Future Treatment of Alzheimer’s Disease

Volume: 22 Issue: 33

Author(s): Daniel I. Perez, Ana Martinez, Carmen Gil and Nuria E. Campillo

Affiliation:

关键词: 乙酰胆碱酯酶，阿尔茨海默病，BACE-1，双靶点药物，胆碱酯酶，大麻，GSK3β，多靶点

摘要: Dementia is one of the main causes of the disease burden in developed regions. According to the World Health Organization (WHO), it will become the world’s second leading cause of death by the middle of the century, overtaking cancer. This will have a dramatic impact on medical care, and have important social and economic implications, unless more effective preventive procedures or treatments become available. Alzheimer’s disease (AD) is the most common cause of dementia, accounting for approximately 50–75% of all dementias worldwide, followed by vascular dementia, mixed dementia, and Lewy body dementia.

Currently, acetylcholinesterase (AChE) inhibitors, such as donepezil, rivastigmine and galantamine are used to treat mild to moderate AD. An alternative therapy for severe AD is memantine, an antagonist of the NMDA-subtype of glutamate receptors. However, these drugs provide only temporary symptom improvement, and do not alter disease progression, except temporarily in some patients.

In recent years different approaches have been developed to provide a more effective treatment for AD. These approached include the discovery of emerging targets and new drugs aiming at a single target, but given the complexity of the disease, different targets may need to be engaged simultaneously. New strategies have explored bitopic inhibitors, for example a single drug that acts on different sites of the acetylcholinesterase enzyme to produce at least two different activities, and multitarget drugs that act on multiple therapeutic targets.

In this review, we explore the journey from a bitopic inhibitor strategy to multitarget drugs for the future treatment of AD.

Cite this article as:

Daniel I. Perez, Ana Martinez, Carmen Gil and Nuria E. Campillo , From Bitopic Inhibitors to Multitarget Drugs for the Future Treatment of Alzheimer’s Disease, Current Medicinal Chemistry 2015; 22 (33) . https://dx.doi.org/10.2174/0929867322666150812145825