Related Experiment Videos
A molecular approach in drug development for Alzheimer's disease
Snezana Agatonovic-Kustrin1, Christine Kettle2, David W Morton2
1School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500, Selangor Darul Ehsan, Malaysia; School of Pharmacy and Applied Science, La Trobe Institute for Molecular Sciences, La Trobe University, Edwards Rd., Bendigo, 3550, Australia.
Abstract:
An increase in dementia numbers and global trends in population aging across the world prompts the need for new medications to treat the complex biological dysfunctions, such as neurodegeneration associated with dementia. Alzheimer's disease (AD) is the most common form of dementia. Cholinergic signaling, which is important in cognition, is slowly lost in AD, so the first line therapy is to treat symptoms with acetylcholinesterase inhibitors to increase levels of acetylcholine. Out of five available FDA-approved AD medications, donepezil, galantamine and rivastigmine are cholinesterase inhibitors while memantine, a N-methyl d-aspartate (NMDA) receptor antagonist, blocks the effects of high glutamate levels. The fifth medication consists of a combination of donepezil and memantine. Although these medications can reduce and temporarily slow down the symptoms of AD, they cannot stop the damage to the brain from progressing. For a superior therapeutic effect, multi-target drugs are required. Thus, a Multi-Target-Directed Ligand (MTDL) strategy has received more attention by scientists who are attempting to develop hybrid molecules that simultaneously modulate multiple biological targets. This review highlights recent examples of the MTDL approach and fragment based strategy in the rational design of new potential AD medications.
Insights
New Alzheimer's disease (AD) medications are needed as current treatments only manage symptoms. A multi-target-directed ligand (MTDL) strategy offers a promising approach for developing advanced AD therapies by targeting multiple biological pathways simultaneously.
Area of Science:
- Neuroscience
- Pharmacology
- Drug Discovery
Background:
- Global population aging drives an increase in dementia cases, particularly Alzheimer's disease (AD).
- Current AD medications like acetylcholinesterase inhibitors and NMDA receptor antagonists offer symptomatic relief but do not halt neurodegeneration.
- There is a critical need for novel therapeutics that can address the complex biological dysfunctions underlying AD progression.
Purpose of the Study:
- To review recent advancements in the development of potential Alzheimer's disease medications.
- To highlight the Multi-Target-Directed Ligand (MTDL) strategy for designing novel therapeutic agents.
- To discuss the application of fragment-based strategies in the rational design of new AD drugs.
Main Methods:
- Review of current literature on Alzheimer's disease therapeutics.
- Analysis of Multi-Target-Directed Ligand (MTDL) approaches in drug design.
- Examination of fragment-based strategies for developing novel drug candidates.
Main Results:
- Current FDA-approved AD medications primarily manage symptoms by targeting cholinergic signaling or glutamate pathways.
- The MTDL strategy enables the design of hybrid molecules that simultaneously modulate multiple biological targets relevant to AD.
- Fragment-based approaches contribute to the rational design of new potential AD medications.
Conclusions:
- Existing Alzheimer's disease treatments provide only temporary symptom management and do not prevent disease progression.
- The MTDL strategy represents a significant advancement in developing more effective Alzheimer's disease therapies.
- Rational drug design, incorporating MTDL and fragment-based approaches, is crucial for discovering superior treatments for Alzheimer's disease.