Alzheimer's Disease: Treatment of Multi-Factorial Disorders with Multi- Target Approach
Baljit Kaur1, Vivesh1, Palwinder Singh1
1Department of Chemistry, Guru Nanak Dev University, Amritsar-143005, India.
Abstract:
Alzheimer's Disease (AD) is a common neurodegenerative disorder that is almost incurable with the existing therapeutic interventions. Due to the high-risk factors associated with this disease, there is a global pursuit of new anti-AD agents. Herein, we explore the biochemical pathways which are responsible for the initiation/propagation of the disease. It is observed that out of the two isoforms of β-secretase, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and β-site amyloid precursor protein cleaving enzyme 2 (BACE2) present in the brain, BACE1 plays the predominant role in the commencement of AD. Moreover, the catalytic activities of acetylcholinesterase and butyrylcholinesterase regulate the concentration of neurotransmitters, and they are needed to be kept under control during the signs of AD. Hence, these two enzymes also serve as potential targets for the treatment of AD patients. Keeping in view the multifactorial nature of the disease, we also reviewed the multitarget approach for the treatment of AD. It is tried to identify the common structural features of those molecules which act on different cellular targets during AD therapy.
Insights
This study reviews Alzheimer's Disease (AD) biochemical pathways, identifying beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) as a key initiator. It also highlights acetylcholinesterase and butyrylcholinesterase as therapeutic targets for new anti-AD agents.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Alzheimer's Disease (AD) is a prevalent neurodegenerative disorder with limited effective treatments.
- High-risk factors necessitate the global search for novel anti-AD therapeutic agents.
- Understanding AD's biochemical pathways is crucial for developing new interventions.
Purpose of the Study:
- To explore biochemical pathways involved in Alzheimer's Disease initiation and propagation.
- To identify key enzymes and targets for potential AD therapeutic strategies.
- To review multitarget approaches for Alzheimer's Disease treatment.
Main Methods:
- Review of scientific literature on Alzheimer's Disease pathogenesis.
- Analysis of the roles of beta-secretase isoforms (BACE1 and BACE2) in AD.
- Investigation of acetylcholinesterase and butyrylcholinesterase as therapeutic targets.
- Exploration of multitarget drug design principles for AD therapy.
Main Results:
- Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is identified as the primary enzyme in AD initiation.
- Acetylcholinesterase and butyrylcholinesterase are confirmed as significant targets for controlling neurotransmitter levels in AD.
- The study emphasizes the potential of multitarget strategies in addressing the complexity of AD.
Conclusions:
- BACE1 is a critical target for preventing Alzheimer's Disease onset.
- Modulating acetylcholinesterase and butyrylcholinesterase activity offers a viable therapeutic avenue for AD.
- A multitarget approach, identifying common structural features of effective molecules, shows promise for comprehensive AD treatment.
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