Alzheimer's Disease: Evolving Therapeutics, Scientific Progress, and Key Challenges

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) aggregation, tau pathology, and neurotoxicity.
• Aβ aggregation is a key pathological hallmark, but its role as a sole therapeutic target is complex and requires further exploration.
• Current therapeutic strategies targeting Aβ aggregation face challenges including poor bioavailability, off-target effects, and limited clinical efficacy.

Purpose of the Study:

• To review the mechanisms of Aβ aggregation in Alzheimer's disease.
• To explore various therapeutic strategies aimed at inhibiting or modulating Aβ aggregation.
• To highlight the importance of multifunctional and targeted treatments for AD.

Main Methods:

• Review of existing literature on Alzheimer's disease pathogenesis and therapeutic interventions.
• Analysis of structure-based inhibitors, small molecules, peptide therapeutics, and immunotherapies targeting Aβ.
• Examination of complementary strategies including metal chelators, β-sheet breakers, molecular chaperones, tau-directed therapies, anti-inflammatory agents, and synaptic modulators.

Main Results:

• Aβ aggregation is a central but not exclusive factor in AD pathogenesis.
• Multiple therapeutic approaches, including small molecules, peptides, and immunotherapy, show promise but face significant hurdles.
• Addressing the multifaceted nature of AD requires exploring diverse targets beyond Aβ, such as tau and neuroinflammation.

Conclusions:

• Effective Alzheimer's disease treatment likely requires multifunctional drugs that target multiple pathological pathways.
• Overcoming the blood-brain barrier and improving drug delivery are critical for therapeutic success.
• Rational drug design and advanced delivery systems are essential for developing next-generation AD therapies.