β-Amyloid precursor protein (APP) and the human diseases

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• The human β-amyloid precursor protein (APP) and its fragments are implicated in numerous diseases, including neurodevelopmental, neurodegenerative, metabolic disorders, and cancer.
• While APP is part of normal physiology, targeting its processing pathways for pharmacological intervention may lead to unintended consequences.
• Alternative splicing (AS) of APP mRNA is increasingly recognized for its significant impact on human disease pathogenesis.

Purpose of the Study:

• To explore the pathophysiological roles of APP in a wide range of human diseases.
• To investigate the potential of targeting APP alternative splicing as a therapeutic strategy.
• To highlight the significance of defective APP mRNA isoforms in disease development.

Main Methods:

• Review of current research on APP functions and its involvement in various diseases.
• Analysis of the impact of alternative splicing on APP's role in human pathology.
• Exploration of potential therapeutic interventions targeting APP splicing events.

Main Results:

• APP and its fragments are involved in diverse conditions, from rare neurodevelopmental disorders to common diseases like Alzheimer's and diabetes.
• Alternative splicing of APP mRNA significantly influences disease mechanisms.
• Defective APP mRNA isoforms are identified as key contributors to cellular and tissue pathology.

Conclusions:

• Targeting APP proteolytic processing requires careful consideration due to potential side effects.
• Alternative splicing of APP presents a promising new direction for therapeutic research.
• Developing molecules to correct or inhibit pathological APP splicing, such as antisense drugs, offers potential future treatments for various diseases.